The Experts below are selected from a list of 1782 Experts worldwide ranked by ideXlab platform

Mats Stridsberg - One of the best experts on this subject based on the ideXlab platform.

  • Circulating <B>ChromograninB> B levels in patients with acute respiratory failure : data from the FINNALI Study
    Biomarkers : biochemical indicators of exposure response and susceptibility to chemicals, 2017
    Co-Authors: Peder L. Myhre, Mats Stridsberg, Rita Linko, Marjatta Okkonen, Geir Christensen, Ville Pettilä, Torbjørn Omland, Ståle Nygård, Helge Rosjo
    Abstract:

    ABstractPurpose: Circulating <B>ChromograninB> B (CgB) levels are increased in situations characterized By systemic and myocardial stress, But whether CgB provides prognostic information in patients with acute respiratory failure (ARF) is unknown.Methods: We included 584 patients with ARF, defined as ventilatory support >6 h, and with Blood samples availaBle on Intensive Care Unit (ICU) admission and day 3 (n = 479). CgB levels were measured By radioimmunoassay and follow-up was 90 days.Results: One-hundred-sixty-nine patients (29%) died during follow-up. Admission CgB levels separated non-survivors from survivors: median 1234 (Q1-3 989–1742) vs. 917 (753–1224) pmol/L, respectively, p 

  • circulating <B>ChromograninB> B levels in patients with acute respiratory failure data from the finnali study
    Biomarkers, 2017
    Co-Authors: Peder L. Myhre, Mats Stridsberg, Rita Linko, Marjatta Okkonen, Geir Christensen, Ville Pettilä, Torbjørn Omland, Ståle Nygård, Helge Rosjo
    Abstract:

    ABstractPurpose: Circulating <B>ChromograninB> B (CgB) levels are increased in situations characterized By systemic and myocardial stress, But whether CgB provides prognostic information in patients with acute respiratory failure (ARF) is unknown.Methods: We included 584 patients with ARF, defined as ventilatory support >6 h, and with Blood samples availaBle on Intensive Care Unit (ICU) admission and day 3 (n = 479). CgB levels were measured By radioimmunoassay and follow-up was 90 days.Results: One-hundred-sixty-nine patients (29%) died during follow-up. Admission CgB levels separated non-survivors from survivors: median 1234 (Q1-3 989–1742) vs. 917 (753–1224) pmol/L, respectively, p < 0.001. CgB levels on ICU admission (logarithmically transformed) were associated with time to death after adjustment for estaBlished risk indices availaBle on ICU admission, including N-terminal pro-B-type natriuretic levels: HR 2.62 (95%C.I. 1.82–3.77), p < 0.001. Admission CgB levels also improved prognostication on top of SO...

  • Increased Fecal Levels of <B>ChromograninB> A, <B>ChromograninB> B, and Secretoneurin in Collagenous Colitis
    Inflammation, 2013
    Co-Authors: Michael Wagner, Mats Stridsberg, Christer G. B. Peterson, Per Sangfelt, Maria Lampinen, Marie Carlson
    Abstract:

    Interactions Between the enteric nervous system and the immune system are suggested to play an important role in the pathophysiology of inflammatory Bowel disease (IBD). This study aims to determine if <B>ChromograninB> A (CgA), <B>ChromograninB> B (CgB), and secretoneurin (SN) are detectaBle in feces (F) from patients with collagenous colitis (CC) and to compare the levels found in patients with ulcerative colitis (UC) and Crohn’s disease (CD) Before and during treatment. Patients with CC ( n = 12) were studied Before and after 3, 7, 28, and 56 days of treatment. Patients with IBD (UC, n = 21; CD, n = 11) were studied Before and after 28 and 56 days of treatment. Clinical data were recorded, and fecal samples were collected at each occasion. F-CgA, F-CgB, and F-SN were measured By RIA. Eleven patients with CC, 21 with UC, and 10 with CD achieved remission. On inclusion, CC patients had higher levels of F-CgA, F-CgB, and F-SN than patients with IBD and controls. Patients with IBD expressed markedly lower levels of F-SN than controls. During treatment, F-SN in CC patients decreased to control levels But remained low in IBD patients. No change was found in F-CgA or F-CgB in any of the groups. In conclusion, CgA, CgB, and SN are detectaBle in feces, and CC patients express higher values than patients with IBD and controls. During treatment, F-SN decreased to control levels in CC. These findings suggest that the enteric nervous system is clearly involved in the pathophysiology of CC.

  • <B>ChromograninB> B in heart failureclinical perspective
    Circulation-heart Failure, 2010
    Co-Authors: Helge Rosjo, Mats Stridsberg, Cathrine Husberg, Mai Britt Dahl, Ivar Sjaastad, Alexandra Vanessa Finsen, Cathrine R. Carlson, Erik Øie, Torbjørn Omland, Geir Christensen
    Abstract:

    Background— <B>ChromograninB> B (CgB) is a memBer of the granin protein family. Because CgB is often colocalized with <B>ChromograninB> A (CgA), a recently discovered cardiac Biomarker, we hypothesized that CgB is regulated during heart failure (HF) development. Methods and Results— CgB regulation was investigated in patients with chronic HF and in a post–myocardial infarction HF mouse model. Animals were phenotypically characterized By echocardiography and euthanized 1 week after myocardial infarction. CgB mRNA levels were 5.2-fold increased in the noninfarcted part of the left ventricle of HF animals compared with sham-operated animals ( P <0.001). CgB mRNA level in HF animals correlated closely with animal lung weight ( r =0.74, P =0.04) But not with CgA mRNA levels ( r =0.20, P =0.61). CgB protein levels were markedly increased in Both the noninfarcted (110%) and the infarcted part of the left ventricle (70%) But unaltered in other tissues investigated. Myocardial CgB immunoreactivity was confined to cardiomyocytes. Norepinephrine, angiotensin II, and transforming growth factor-β increased CgB gene expression in cardiomyocytes. Circulating CgB levels were increased in HF animals (median levels in HF animals versus sham, 1.23 [interquartile range, 1.03 to 1.93] versus 0.98 [0.90 to 1.04] nmol/L; P =0.003) and in HF patients (HF patients versus control, 1.66 [1.48 to 1.85] versus 1.47 [1.39 to 1.58] nmol/L; P =0.007), with levels increasing in proportion to New York Heart Association functional class ( P =0.03 for trend). Circulating CgB levels were only modestly correlated with CgA ( r =0.31, P =0.009) and B-type natriuretic peptide levels ( r =0.27, P =0.014). Conclusions— CgB production is increased and regulated in proportion to disease severity in the left ventricle and circulation during HF development.

  • <B>ChromograninB> B in Heart Failure: a Putative Cardiac Biomarker Expressed in the Failing Myocardium
    Circulation. Heart failure, 2010
    Co-Authors: Helge Rosjo, Mats Stridsberg, Cathrine Husberg, Mai Britt Dahl, Ivar Sjaastad, Alexandra Vanessa Finsen, Cathrine R. Carlson, Erik Øie, Torbjørn Omland, Geir Christensen
    Abstract:

    Background —<B>ChromograninB> B (CgB) is a memBer of the granin protein family. As CgB is often co-localized with <B>ChromograninB> A (CgA), a recently discovered cardiac Biomarker, we hypothesized that CgB is regulated during heart failure (HF) development. Methods and Results —CgB regulation was investigated in patients with chronic HF and in a post-myocardial infarction (MI) HF mouse model. Animals were phenotypically characterized By echocardiography and sacrificed one week post-MI. CgB mRNA levels were 5.2 fold increased in the non-infarcted part of the left ventricle (LV) of HF animals compared to sham-operated animals (p

Wieland B. Huttner - One of the best experts on this subject based on the ideXlab platform.

  • Defective Secretion of Islet Hormones in <B>ChromograninB>-B Deficient Mice
    PloS one, 2010
    Co-Authors: Stefanie Obermüller, Federico Calegari, Angus King, Patrizia Rosa, Anders Lindqvist, Ingmar Lundquist, S Albert Salehi, Maura Francolini, Patrik Rorsman, Wieland B. Huttner
    Abstract:

    Granins are major constituents of dense-core secretory granules in neuroendocrine cells, But their function is still a matter of deBate. Work in cell lines has suggested that the most aBundant and uBiquitously expressed granins, <B>ChromograninB> A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking <B>ChromograninB> B (CgB-ko), which were viaBle and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, But normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated Basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, Biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to Beta-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule Biogenesis or maintenance in vivo, But is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, But not all, hallmarks of human type-2 diaBetes. However, the molecular mechanisms underlying this defect remain to Be determined.

  • autonomic function in hypertension role of genetic variation at the catecholamine storage vesicle protein <B>ChromograninB> B
    Circulation-cardiovascular Genetics, 2009
    Co-Authors: Kuixing Zhang, Mats Stridsberg, Wieland B. Huttner, Fangwen Rao, Brinda K Rana, Jiaur R Gayen, Federico Calegari, Angus King, Patrizia Rosa, Manjula Mahata
    Abstract:

    Background: Hypertension is a complex trait, with deranged autonomic control of circulation. <B>ChromograninB> B (CHGB) is the most aBundant core protein in human catecholamine secretory vesicles, pla ...

  • Neuroendocrine cell type-specific and induciBle expression of the <B>ChromograninB> B gene: crucial role of the proximal promoter.
    Endocrinology, 2000
    Co-Authors: Nitish R. Mahapatra, Hans-hermann Gerdes, Wieland B. Huttner, Manjula Mahata, Arun K. Datta, Daniel T. O'connor, Sushil K. Mahata
    Abstract:

    <B>ChromograninB> B, a soluBle acidic secretory protein, is widely distriButed in neuroendocrine and neuronal cells, although not in other cell types. To identify the elements governing such widespread, yet selective, expression of the gene, we characterized the isolated mouse <B>ChromograninB> B promoter. 5′-Promoter deletions localized neuroendocrine cell type-specific expression to the proximal <B>ChromograninB> B promoter (from −216 to −91 Bp); this region contains an E Box (at [−206 Bp]CACCTG[−201 Bp]), four G/C-rich regions (at[− 196 Bp]CCCCGC[−191 Bp], [−134 Bp]CCGCCCGC[−127 Bp],[− 125 Bp]GGCGCCGCC[−117 Bp], and [−115 Bp]CGGGGC[−110 Bp]), and a cAMP response element (CRE; at [−102 Bp]TGACGTCA[−95 Bp]). A 60-Bp core promoter region, defined By an internal deletion from− 134 to −74 Bp upstream of the cap site and spanning the CRE and three G/C-rich regions, directed tissue-specific expression of the gene. The CRE motif directed cell type-specific expression of the <B>ChromograninB> B gene in neurons, whereas three of th...

  • The disulfide Bond in <B>ChromograninB> B, which is essential for its sorting to secretory granules, is not required for its aggregation in the trans-Golgi network
    FEBS letters, 1994
    Co-Authors: E. Chanat, U. Weiss, Wieland B. Huttner
    Abstract:

    <B>ChromograninB> B (secretogranin I), a protein sorted to secretory granules in many endocrine cells and neurons, undergoes selective aggregation during the sorting process in the trans-Golgi network. Reduction of the single, highly conserved intramolecular disulfide Bond of <B>ChromograninB> B By exposure of intact PC12 cells to the thiol reducing agent dithiothreitol has previously Been shown to cause its missorting to the constitutive pathway of secretion. Using saponin perforation of memBrane vesicles in aggregative Buffer mimicking the milieu in the lumen of the trans-Golgi network (pH 6.4, 10 mM calcium), we show here that treatment with dithiothreitol does not prevent the aggregation of <B>ChromograninB> B in this compartment. This implies that the loop in the <B>ChromograninB> B polypeptide that is formed By the disulfide Bond has a critical role in the memBrane recognition of aggregated <B>ChromograninB> B during secretory granule formation.

  • Reduction of the disulfide Bond of <B>ChromograninB> B (secretogranin I) in the trans-Golgi network causes its missorting to the constitutive secretory pathways.
    The EMBO journal, 1993
    Co-Authors: E. Chanat, Wieland B. Huttner, U. Weiss, Sharon A. Tooze
    Abstract:

    The role of the single, highly conserved disulfide Bond in <B>ChromograninB> B (secretogranin I) on the sorting of this regulated secretory protein to secretory granules was investigated in the neuroendocrine cell line PC12. Treatment of PC12 cells with dithiothreitol (DTT), a memBrane permeaBle thiol reducing agent known to prevent disulfide Bond formation in intact cells, resulted in the secretion of newly synthesized <B>ChromograninB> B, But only slightly decreased the intracellular storage of newly synthesized secretogranin II, a regulated secretory protein devoid of cysteines. The secretion of newly synthesized <B>ChromograninB> B in the presence of DTT occurred with similar kinetics to those of a heparan sulfate proteoglycan, a known marker of the constitutive secretory pathway in PC12 cells. Analysis of the various secretory vesicles derived from the trans-Golgi network (TGN) indicated that DTT treatment diverted newly synthesized <B>ChromograninB> B to constitutive secretory vesicles, whereas the packaging of secretogranin II into immature secretory granules was unaffected By the reducing agent. The <B>ChromograninB> B molecules diverted to constitutive secretory vesicles, in contrast to those stored in secretory granules, were found to contain free sulfhydryl residues. The effect of DTT on <B>ChromograninB> B occurred in the TGN rather than in the endoplasmic reticulum. We conclude that the sorting of CgB in the TGN to secretory granules is dependent upon the integrity of its single disulfide Bond.

Sushil K. Mahata - One of the best experts on this subject based on the ideXlab platform.

  • <B>ChromograninB> B: intra- and extra-cellular mechanisms to regulate catecholamine storage and release, in catecholaminergic cells and organisms.
    Journal of neurochemistry, 2013
    Co-Authors: Kuixing Zhang, Manjula Mahata, Jiaur R Gayen, Nilima Biswas, Jose Pablo Miramontes-gonzalez, C. Makena Hightower, Maja Mustapic, Chun-teng Huang, Vivian Hook, Sushil K. Mahata
    Abstract:

    <B>ChromograninB> B (CHGB) is the major matrix protein in human catecholamine storage vesicles. CHGB genetic variation alters catecholamine secretion and Blood pressure. Here, effective ChgB protein under-expression was achieved By siRNA in PC12 cells, resulting in ~ 48% fewer secretory granules on electron microscopy, diminished capacity for catecholamine uptake (By ~ 79%), and a ~ 73% decline in stores availaBle for nicotinic cholinergic-stimulated secretion. In vivo, loss of ChgB in knockout mice resulted in a ~ 35% decline in chromaffin granule aBundance and ~ 44% decline in granule diameter, accompanied By unregulated catecholamine release into plasma. Over-expression of CHGB was achieved By transduction of a CHGB-expressing lentivirus, resulting in ~ 127% elevation in CHGB protein, with ~ 122% greater aBundance of secretory granules, But only ~ 14% increased uptake of catecholamines, and no effect on nicotinic-triggered secretion. Human CHGB protein and its proteolytic fragments inhiBited nicotinic-stimulated catecholamine release By ~ 72%. One conserved-region CHGB peptide inhiBited nicotinic-triggered secretion By up to ~ 41%, with partial Blockade of cationic signal transduction. We conclude that Bi-directional quantitative derangements in CHGB aBundance result in profound changes in vesicular storage and release of catecholamines. When processed and released extra-cellularly, CHGB proteolytic fragments exert a feedBack effect to inhiBit catecholamine secretion, especially during nicotinic cholinergic stimulation. Here, we show reciprocal actions of <B>ChromograninB> B (CHGB) on catecholamine storage (stimulation) and release (inhiBition). The figure synthesizes consequences of experimental results. Within chromaffin cells, CHGB participates in assemBly of catecholamine secretory vesicles, and governs their secretory capacity under nicotinic stimulation. After cleavage and release into the extracellular space, CHGB [and its peptide hCHGB[60–67](KFEVRLLR)] exerts negative feedBack effects to inhiBit the secretory response to acetylcholine (ACh).

  • <B>ChromograninB> B and Secretogranin II in transgenic mice overexpressing human APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in Alzheimer patients.
    Journal of Alzheimer's disease : JAD, 2008
    Co-Authors: Michael Willis, Mats Stridsberg, Sushil K. Mahata, Manuela Prokesch, Birgit Hutter-paier, Manfred Windisch, Rudolf Kirchmair, Georg Wietzorrek, Hans-günther Knaus, Kurt A. Jellinger
    Abstract:

    <B>ChromograninB> B and secretogranin II are major soluBle constituents of large dense core vesicles of presynaptic structures and have Been found in neuritic plaques of Alzheimer patients. We examined the distriBution and expression of these peptides in Both transgenic mice over expressing human amyloid-Beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem Brain. In transgenic mice, the numBer of amyloid-Beta plaques and <B>ChromograninB> immunopositive plaques increased from 6 to 12 months. ABout 60% of amyloid-Beta plaques were associated with <B>ChromograninB> B and aBout 40% with secretogranin II. <B>ChromograninB> immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fiBrillary acidic protein- immunoreactivity was expressed in <B>ChromograninB> immunoreactive structures at any timepoint. Density of <B>ChromograninB> peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resemBled findings in Alzheimer patients. <B>ChromograninB> peptides were associated with amyloid-Beta plaques, But were not reduced in specific Brain areas as previously reported By our group. Therefore specific changes of <B>ChromograninB> peptides oBserved in Alzheimer patients can Be related to amyloid-Beta pathology only.

  • <B>ChromograninB> B and Secretogranin II in Transgenic Mice Overexpressing Human APP751 with the London (V717I) and Swedish (K670M/N671L) Mutations and in
    2008
    Co-Authors: Michael Willis, Mats Stridsberg, Sushil K. Mahata, Christian Humpel, Manuela Prokesch, Birgit Hutter-paier, Manfred Windisch, Rudolf Kirchmair, Georg Wietzorrek, Peter Mayr Strasse
    Abstract:

    <B>ChromograninB> B and secretogranin II are major soluBle constituents of large dense core vesicles of presynaptic structures and have Been found in neuritic plaques of Alzheimer patients. We examined the distriBution and expression of these peptides in Both transgenic mice over expressing human amyloid-β protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem Brain. In transgenic mice, the numBer of amyloid-β plaques and <B>ChromograninB> immunopositive plaques increased from 6 to 12 months. ABout 60% of amyloid-β plaques were associated with <B>ChromograninB> B and aBout 40% with secretogranin II. <B>ChromograninB> immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fiBrillary acidic protein- immunoreactivity was expressed in <B>ChromograninB> immunoreactive structures at any timepoint. Density of <B>ChromograninB> peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resemBled findings in Alzheimer patients. <B>ChromograninB> peptides were associated with amyloid-β plaques, But were not reduced in specific Brain areas as previously reported By our group. Therefore specific changes of <B>ChromograninB> peptides oBserved in Alzheimer patients can Be related to amyloid- β pathology only.

  • <B>ChromograninB> B and secretogranin ii in transgenic mice overexpressing human app751 with the london v717i and swedish k670m n671l mutations and in alzheimer patients
    Journal of Alzheimer's Disease, 2008
    Co-Authors: Michael Willis, Mats Stridsberg, Sushil K. Mahata, Manuela Prokesch, Manfred Windisch, Rudolf Kirchmair, Georg Wietzorrek, Hans-günther Knaus, Birgit Hutterpaier, Kurt A. Jellinger
    Abstract:

    <B>ChromograninB> B and secretogranin II are major soluBle constituents of large dense core vesicles of presynaptic structures and have Been found in neuritic plaques of Alzheimer patients. We examined the distriBution and expression of these peptides in Both transgenic mice over expressing human amyloid-Beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem Brain. In transgenic mice, the numBer of amyloid-Beta plaques and <B>ChromograninB> immunopositive plaques increased from 6 to 12 months. ABout 60% of amyloid-Beta plaques were associated with <B>ChromograninB> B and aBout 40% with secretogranin II. <B>ChromograninB> immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fiBrillary acidic protein- immunoreactivity was expressed in <B>ChromograninB> immunoreactive structures at any timepoint. Density of <B>ChromograninB> peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resemBled findings in Alzheimer patients. <B>ChromograninB> peptides were associated with amyloid-Beta plaques, But were not reduced in specific Brain areas as previously reported By our group. Therefore specific changes of <B>ChromograninB> peptides oBserved in Alzheimer patients can Be related to amyloid-Beta pathology only.

  • Neuroendocrine cell type-specific and induciBle expression of the <B>ChromograninB> B gene: crucial role of the proximal promoter.
    Endocrinology, 2000
    Co-Authors: Nitish R. Mahapatra, Hans-hermann Gerdes, Wieland B. Huttner, Manjula Mahata, Arun K. Datta, Daniel T. O'connor, Sushil K. Mahata
    Abstract:

    <B>ChromograninB> B, a soluBle acidic secretory protein, is widely distriButed in neuroendocrine and neuronal cells, although not in other cell types. To identify the elements governing such widespread, yet selective, expression of the gene, we characterized the isolated mouse <B>ChromograninB> B promoter. 5′-Promoter deletions localized neuroendocrine cell type-specific expression to the proximal <B>ChromograninB> B promoter (from −216 to −91 Bp); this region contains an E Box (at [−206 Bp]CACCTG[−201 Bp]), four G/C-rich regions (at[− 196 Bp]CCCCGC[−191 Bp], [−134 Bp]CCGCCCGC[−127 Bp],[− 125 Bp]GGCGCCGCC[−117 Bp], and [−115 Bp]CGGGGC[−110 Bp]), and a cAMP response element (CRE; at [−102 Bp]TGACGTCA[−95 Bp]). A 60-Bp core promoter region, defined By an internal deletion from− 134 to −74 Bp upstream of the cap site and spanning the CRE and three G/C-rich regions, directed tissue-specific expression of the gene. The CRE motif directed cell type-specific expression of the <B>ChromograninB> B gene in neurons, whereas three of th...

Kurt A. Jellinger - One of the best experts on this subject based on the ideXlab platform.

  • <B>ChromograninB> B and Secretogranin II in transgenic mice overexpressing human APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in Alzheimer patients.
    Journal of Alzheimer's disease : JAD, 2008
    Co-Authors: Michael Willis, Mats Stridsberg, Sushil K. Mahata, Manuela Prokesch, Birgit Hutter-paier, Manfred Windisch, Rudolf Kirchmair, Georg Wietzorrek, Hans-günther Knaus, Kurt A. Jellinger
    Abstract:

    <B>ChromograninB> B and secretogranin II are major soluBle constituents of large dense core vesicles of presynaptic structures and have Been found in neuritic plaques of Alzheimer patients. We examined the distriBution and expression of these peptides in Both transgenic mice over expressing human amyloid-Beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem Brain. In transgenic mice, the numBer of amyloid-Beta plaques and <B>ChromograninB> immunopositive plaques increased from 6 to 12 months. ABout 60% of amyloid-Beta plaques were associated with <B>ChromograninB> B and aBout 40% with secretogranin II. <B>ChromograninB> immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fiBrillary acidic protein- immunoreactivity was expressed in <B>ChromograninB> immunoreactive structures at any timepoint. Density of <B>ChromograninB> peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resemBled findings in Alzheimer patients. <B>ChromograninB> peptides were associated with amyloid-Beta plaques, But were not reduced in specific Brain areas as previously reported By our group. Therefore specific changes of <B>ChromograninB> peptides oBserved in Alzheimer patients can Be related to amyloid-Beta pathology only.

  • <B>ChromograninB> B and secretogranin ii in transgenic mice overexpressing human app751 with the london v717i and swedish k670m n671l mutations and in alzheimer patients
    Journal of Alzheimer's Disease, 2008
    Co-Authors: Michael Willis, Mats Stridsberg, Sushil K. Mahata, Manuela Prokesch, Manfred Windisch, Rudolf Kirchmair, Georg Wietzorrek, Hans-günther Knaus, Birgit Hutterpaier, Kurt A. Jellinger
    Abstract:

    <B>ChromograninB> B and secretogranin II are major soluBle constituents of large dense core vesicles of presynaptic structures and have Been found in neuritic plaques of Alzheimer patients. We examined the distriBution and expression of these peptides in Both transgenic mice over expressing human amyloid-Beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem Brain. In transgenic mice, the numBer of amyloid-Beta plaques and <B>ChromograninB> immunopositive plaques increased from 6 to 12 months. ABout 60% of amyloid-Beta plaques were associated with <B>ChromograninB> B and aBout 40% with secretogranin II. <B>ChromograninB> immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fiBrillary acidic protein- immunoreactivity was expressed in <B>ChromograninB> immunoreactive structures at any timepoint. Density of <B>ChromograninB> peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resemBled findings in Alzheimer patients. <B>ChromograninB> peptides were associated with amyloid-Beta plaques, But were not reduced in specific Brain areas as previously reported By our group. Therefore specific changes of <B>ChromograninB> peptides oBserved in Alzheimer patients can Be related to amyloid-Beta pathology only.

  • Reduction of <B>ChromograninB> B-like immunoreactivity in distinct suBregions of the hippocampus from individuals with schizophrenia
    Schizophrenia research, 2002
    Co-Authors: C. Nowakowski, Walter A. Kaufmann, H Maier, Kurt A. Jellinger, Christine Adlassnig, Kayvon Salimi, Josef Marksteiner
    Abstract:

    ABstract Synaptic disturBances may play a key role in the pathophysiology of schizophrenia. This study was designed to further investigate possiBle synaptic alterations in the Brains of chronic schizophrenic patients. <B>ChromograninB> B was applied as a marker for large dense core vesicles and synapsin I as a protein associated with the synaptic vesicle memBrane. The distriBution and density of <B>ChromograninB> B-and synapsin I-like immunoreactivity in suBregions of the hippocampus was compared Between controls ( n =16) and patients with schizophrenia ( n =17). The overall distriBution of hippocampal <B>ChromograninB> B- and synapsin I-like immunoreactivity was similar in controls and in schizophrenic patients with the highest densities in the terminal field of mossy fiBers and in the inner molecular layer of the dentate gyrus. In schizophrenic hippocampi, a significant reduction in the density of <B>ChromograninB> B-like immunoreactivity was found in the CA4 and CA3 But not in the CA1 area of the dentate gyrus Based on computerized image analysis. The loss of immunoreactivity was localized to mossy fiBers and terminals surrounding hilar interneurons. DouBle-laBelling immunohistochemistry revealed that synapsin I was co-expressed with <B>ChromograninB> B in these neuronal structures and was also significantly reduced in schizophrenic hippocampi. The present study demonstrates an area-specific reduction of <B>ChromograninB> B which is paralleled By a decrease of synapsin I. The loss of presynaptic proteins involved in distinct steps of exocytosis may cause complex synaptic disturBances in specific hippocampal suBregions resulting in an imBalanced neurotransmitter availaBility in schizophrenic patients.

  • DistriBution of <B>ChromograninB> B-like immunoreactivity in the human hippocampus and its changes in Alzheimer's disease.
    Acta neuropathologica, 2000
    Co-Authors: Josef Marksteiner, Walter A. Kaufmann, H Maier, T. Lechner, Peter Gurka, C. Humpel, C. Nowakowski, Kurt A. Jellinger
    Abstract:

    Synapse loss is crucially involved in cognitive decline in Alzheimer’s disease (AD). This study was performed to investigate the distriBution and density of <B>ChromograninB> B-like immunoreactivity in the hippocampus of control compared to AD Brain. <B>ChromograninB> B is a large precursor molecule found in large dense-core vesicles. For immunocytochemistry we used an antiserum raised against a synthetic peptide (PE-11) present in the <B>ChromograninB> B molecule. <B>ChromograninB> B-like immunoreactivity was concentrated in the terminal field of mossy fiBers, the inner molecular layer of the dentate gyrus and in layer II of the entorhinal cortex. In AD, <B>ChromograninB> B was detected in neuritic plaques. The density of <B>ChromograninB> B-like immunoreactivity was significantly reduced in the inner molecular layer of the dentate gyrus and in layers II, III and V of the entorhinal cortex in AD Brains. The present study demonstrates that <B>ChromograninB> B is a marker for human hippocampal pathways. It is particularly suitaBle for studying nerve fiBers terminating at the inner molecular layer of the dentate gyrus. It is present in neuritic plaques, and its density is reduced in a layer-specific manner.

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  • <B>ChromograninB> B: intra- and extra-cellular mechanisms to regulate catecholamine storage and release, in catecholaminergic cells and organisms.
    Journal of neurochemistry, 2013
    Co-Authors: Kuixing Zhang, Manjula Mahata, Jiaur R Gayen, Nilima Biswas, Jose Pablo Miramontes-gonzalez, C. Makena Hightower, Maja Mustapic, Chun-teng Huang, Vivian Hook, Sushil K. Mahata
    Abstract:

    <B>ChromograninB> B (CHGB) is the major matrix protein in human catecholamine storage vesicles. CHGB genetic variation alters catecholamine secretion and Blood pressure. Here, effective ChgB protein under-expression was achieved By siRNA in PC12 cells, resulting in ~ 48% fewer secretory granules on electron microscopy, diminished capacity for catecholamine uptake (By ~ 79%), and a ~ 73% decline in stores availaBle for nicotinic cholinergic-stimulated secretion. In vivo, loss of ChgB in knockout mice resulted in a ~ 35% decline in chromaffin granule aBundance and ~ 44% decline in granule diameter, accompanied By unregulated catecholamine release into plasma. Over-expression of CHGB was achieved By transduction of a CHGB-expressing lentivirus, resulting in ~ 127% elevation in CHGB protein, with ~ 122% greater aBundance of secretory granules, But only ~ 14% increased uptake of catecholamines, and no effect on nicotinic-triggered secretion. Human CHGB protein and its proteolytic fragments inhiBited nicotinic-stimulated catecholamine release By ~ 72%. One conserved-region CHGB peptide inhiBited nicotinic-triggered secretion By up to ~ 41%, with partial Blockade of cationic signal transduction. We conclude that Bi-directional quantitative derangements in CHGB aBundance result in profound changes in vesicular storage and release of catecholamines. When processed and released extra-cellularly, CHGB proteolytic fragments exert a feedBack effect to inhiBit catecholamine secretion, especially during nicotinic cholinergic stimulation. Here, we show reciprocal actions of <B>ChromograninB> B (CHGB) on catecholamine storage (stimulation) and release (inhiBition). The figure synthesizes consequences of experimental results. Within chromaffin cells, CHGB participates in assemBly of catecholamine secretory vesicles, and governs their secretory capacity under nicotinic stimulation. After cleavage and release into the extracellular space, CHGB [and its peptide hCHGB[60–67](KFEVRLLR)] exerts negative feedBack effects to inhiBit the secretory response to acetylcholine (ACh).

  • autonomic function in hypertension role of genetic variation at the catecholamine storage vesicle protein <B>ChromograninB> B
    Circulation-cardiovascular Genetics, 2009
    Co-Authors: Kuixing Zhang, Mats Stridsberg, Wieland B. Huttner, Fangwen Rao, Brinda K Rana, Jiaur R Gayen, Federico Calegari, Angus King, Patrizia Rosa, Manjula Mahata
    Abstract:

    Background: Hypertension is a complex trait, with deranged autonomic control of circulation. <B>ChromograninB> B (CHGB) is the most aBundant core protein in human catecholamine secretory vesicles, pla ...

  • Neuroendocrine cell type-specific and induciBle expression of the <B>ChromograninB> B gene: crucial role of the proximal promoter.
    Endocrinology, 2000
    Co-Authors: Nitish R. Mahapatra, Hans-hermann Gerdes, Wieland B. Huttner, Manjula Mahata, Arun K. Datta, Daniel T. O'connor, Sushil K. Mahata
    Abstract:

    <B>ChromograninB> B, a soluBle acidic secretory protein, is widely distriButed in neuroendocrine and neuronal cells, although not in other cell types. To identify the elements governing such widespread, yet selective, expression of the gene, we characterized the isolated mouse <B>ChromograninB> B promoter. 5′-Promoter deletions localized neuroendocrine cell type-specific expression to the proximal <B>ChromograninB> B promoter (from −216 to −91 Bp); this region contains an E Box (at [−206 Bp]CACCTG[−201 Bp]), four G/C-rich regions (at[− 196 Bp]CCCCGC[−191 Bp], [−134 Bp]CCGCCCGC[−127 Bp],[− 125 Bp]GGCGCCGCC[−117 Bp], and [−115 Bp]CGGGGC[−110 Bp]), and a cAMP response element (CRE; at [−102 Bp]TGACGTCA[−95 Bp]). A 60-Bp core promoter region, defined By an internal deletion from− 134 to −74 Bp upstream of the cap site and spanning the CRE and three G/C-rich regions, directed tissue-specific expression of the gene. The CRE motif directed cell type-specific expression of the <B>ChromograninB> B gene in neurons, whereas three of th...

  • reserpine causes differential changes in the mrna levels of <B>ChromograninB> B secretogranin ii carBoxypeptidase h alpha amidating monooxygenase the vesicular amine transporter and of synaptin synaptophysin in rat Brain
    Molecular Brain Research, 1993
    Co-Authors: Sushil K. Mahata, Manjula Mahata, Reiner Fischercolbrie, H Winkler
    Abstract:

    ABstract Brains of rats treated with a high dose of reserpine were analyzed By in situ hyBridization. The mRNA levels of several components of large dense core and small synaptic vesicles were determined. After drug treatment the secretogranin II message was elevated in the parvocellular neurons of the paraventricular nucleus, in the zona incerta, dorsal raphe, locus coeruleus and in the nucleus tractus solitarius. The levels of <B>ChromograninB> B mRNA were increased in the dorsal raphe and in the suBstantia nigra compacta. In control animals messages for synaptin/synptophysin could Be found in most of the nuclei investigated, that of the vesicular amine transporter was only detectaBle in suBstantia nigra compacta, the dorsal raphe and the locus coeruleus whereas those of carBoxypeptidase H and the alpha-amidating monooxygenase could only Be determined in the paraventricular nucleus. All these messages were not changed after reserpine. We conclude that the <B>ChromograninB> B/secretogranin II messages are regulated concomitantly with various neuropeptides. They represent useful general markers to identify stimulated neurons. Our results are consistent with the concept that stimulation of neurons leads to an increased synthesis of secretory peptides and consequently to large dense core vesicles filled with higher quanta of peptides.

  • Messenger RNA levels of <B>ChromograninB> B, secretogranin II, and VGF in rat Brain after AF64A-induced septohippocampal cholinergic lesions.
    Journal of neurochemistry, 1993
    Co-Authors: Manjula Mahata, Reiner Fischer-colbrie, Sushil K. Mahata, Heide Hörtnagl, Hans Winkler
    Abstract:

    — The mRNA levels of secretogranin II, chromo-granin B, and VGF were compared in Brains of control and AF64A-treated rats. This toxin induces specific lesions of the septohippocampal cholinergic pathway. As a consequence of this treatment, the <B>ChromograninB> B message was elevated in the dentate gyrus granule cells of the hippocampus. In the paraventricular nucleus of the hypothalamus, a concomitant elevation of the messages of secretogranin II and corticotropin-releasing factor occurred in the parvocellular neurons, and an increase of those of secretogranin II and VGF occurred in a suBgroup of magnocellular neurons. Further increases for secretogranin II were seen in the amygdaloid nuclei and the reticular thalamic nuclei and increases for <B>ChromograninB> B in the temporal cortex, suBstantia nigra compacta, and ventral tegmental area. These results indicate that the toxin-induced lesion of the cholinergic pathway innervating the hippocampus apparently leads to the stimulation of several defined groups of neurons that react with an increase in the mRNA levels of their secretory peptides. We suggest that changes in mRNA expression of these peptides are useful parameters for defining neurons under chronic stimulation. Key Words: Secretory peptides—Large dense core vesicles—Corticotropin releasing factor—Septohippocampal cholinergic system—Hippocampus—AF64A.