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Vijayalakshmi Ravindranath - One of the best experts on this subject based on the ideXlab platform.

  • Human brain thioltransferase: constitutive expression and localization by fluorescence in situ hybridization.
    Molecular Brain Research, 2000
    Co-Authors: Sadguna Y. Balijepalli, Michael R. Boyd, Vijayalakshmi Ravindranath
    Abstract:

    Thioltransferase (glutaredoxin) is a member of the family of thiol-disulfide oxido-reductases that maintain the sulfhydryl homeostasis in Cells by catalyzing thiol-disulfide interchange reactions. One of the major consequences of oxidative stress in brain is formation of protein-glutathione mixed disulfide (through oxidation of protein thiols) which can be reversed by thioltransferase during recovery of brain from oxidative stress. Here we have visualized the location of thioltransferase in brain regions from seven human tissues obtained at autopsy. Constitutively expressed thioltransferase activity was detectable in all human brains examined although inter-individual variations were seen. The enzyme activity was significantly higher in hippocampus and Cerebellum as compared to other regions. Constitutive expression of thioltransferase mRNA was detectable by Northern blot analysis. Localization of thioltransferase mRNA by fluorescence in situ hybridization revealed its presence predominantly in neurons in the cerebral cortex, Purkinje and Granule Cell layers of the Cerebellum, Granule Cell layer of the dentate gyrus and in the pyramidal neurons of CA1, CA2 and CA3 subfields of hippocampus. These discrete neuronal concentrations of thioltransferase would be consistent with an essential role in modulating recovery of protein thiols from mixed disulfides formed during oxidative stress.

  • Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridization.
    Archives of biochemistry and biophysics, 2000
    Co-Authors: Sudarshan C. Upadhya, Michael R. Boyd, Padmashree S. Tirumalai, Toshiyuki Mori, Vijayalakshmi Ravindranath
    Abstract:

    Cytochrome P4502E (P4502E), the major ethanol-inducible P450 metabolizes ethanol to acetaldehyde and bioactivates procarcinogens to ultimate carcinogens. Metabolism of ethanol to acetaldehyde in the brain could be deleterious since it can react with cytoskeletal proteins, forming adducts. In the present study, rats were administered ethanol chronically to evaluate its effect on chlorzoxazone hydroxylation in rat brain regions. Chlorzoxazone hydroxylation in brains from the treated rats was induced in hippocampus and cortex, downregulated in brainstem, and unchanged in Cerebellum, striatum, and thalamus. The presence of functionally active P4502E was also seen in human brain regions obtained at autopsy from traffic accident victims. Northern blot analysis of rat and human brain poly(A)(+) RNA hybridized with cDNA to rat CYP2E1 revealed the constitutive presence of a corresponding transcript in rat and human brain. Localization of CYP2E by fluorescence in situ hybridization demonstrated the constitutive expression of CYP2E preferentially in the neuronal Cells in rat and human brain. CYP2E expression was seen in neurons within the cerebral cortex, Purkinje and Granule Cell layers of Cerebellum, Granule Cell layer of dentate gyrus, and pyramidal neurons of CA1, CA2, and CA3 subfields of hippocampus in both rat and human brain. The present studies demonstrate constitutive expression of P4502E1 in brain, its differential induction in rat brain regions by chronic ethanol treatment, and its topographic distribution in rat and human brain.

Sudarshan C. Upadhya - One of the best experts on this subject based on the ideXlab platform.

  • Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridization.
    Archives of biochemistry and biophysics, 2000
    Co-Authors: Sudarshan C. Upadhya, Michael R. Boyd, Padmashree S. Tirumalai, Toshiyuki Mori, Vijayalakshmi Ravindranath
    Abstract:

    Cytochrome P4502E (P4502E), the major ethanol-inducible P450 metabolizes ethanol to acetaldehyde and bioactivates procarcinogens to ultimate carcinogens. Metabolism of ethanol to acetaldehyde in the brain could be deleterious since it can react with cytoskeletal proteins, forming adducts. In the present study, rats were administered ethanol chronically to evaluate its effect on chlorzoxazone hydroxylation in rat brain regions. Chlorzoxazone hydroxylation in brains from the treated rats was induced in hippocampus and cortex, downregulated in brainstem, and unchanged in Cerebellum, striatum, and thalamus. The presence of functionally active P4502E was also seen in human brain regions obtained at autopsy from traffic accident victims. Northern blot analysis of rat and human brain poly(A)(+) RNA hybridized with cDNA to rat CYP2E1 revealed the constitutive presence of a corresponding transcript in rat and human brain. Localization of CYP2E by fluorescence in situ hybridization demonstrated the constitutive expression of CYP2E preferentially in the neuronal Cells in rat and human brain. CYP2E expression was seen in neurons within the cerebral cortex, Purkinje and Granule Cell layers of Cerebellum, Granule Cell layer of dentate gyrus, and pyramidal neurons of CA1, CA2, and CA3 subfields of hippocampus in both rat and human brain. The present studies demonstrate constitutive expression of P4502E1 in brain, its differential induction in rat brain regions by chronic ethanol treatment, and its topographic distribution in rat and human brain.

Michael R. Boyd - One of the best experts on this subject based on the ideXlab platform.

  • Human brain thioltransferase: constitutive expression and localization by fluorescence in situ hybridization.
    Molecular Brain Research, 2000
    Co-Authors: Sadguna Y. Balijepalli, Michael R. Boyd, Vijayalakshmi Ravindranath
    Abstract:

    Thioltransferase (glutaredoxin) is a member of the family of thiol-disulfide oxido-reductases that maintain the sulfhydryl homeostasis in Cells by catalyzing thiol-disulfide interchange reactions. One of the major consequences of oxidative stress in brain is formation of protein-glutathione mixed disulfide (through oxidation of protein thiols) which can be reversed by thioltransferase during recovery of brain from oxidative stress. Here we have visualized the location of thioltransferase in brain regions from seven human tissues obtained at autopsy. Constitutively expressed thioltransferase activity was detectable in all human brains examined although inter-individual variations were seen. The enzyme activity was significantly higher in hippocampus and Cerebellum as compared to other regions. Constitutive expression of thioltransferase mRNA was detectable by Northern blot analysis. Localization of thioltransferase mRNA by fluorescence in situ hybridization revealed its presence predominantly in neurons in the cerebral cortex, Purkinje and Granule Cell layers of the Cerebellum, Granule Cell layer of the dentate gyrus and in the pyramidal neurons of CA1, CA2 and CA3 subfields of hippocampus. These discrete neuronal concentrations of thioltransferase would be consistent with an essential role in modulating recovery of protein thiols from mixed disulfides formed during oxidative stress.

  • Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridization.
    Archives of biochemistry and biophysics, 2000
    Co-Authors: Sudarshan C. Upadhya, Michael R. Boyd, Padmashree S. Tirumalai, Toshiyuki Mori, Vijayalakshmi Ravindranath
    Abstract:

    Cytochrome P4502E (P4502E), the major ethanol-inducible P450 metabolizes ethanol to acetaldehyde and bioactivates procarcinogens to ultimate carcinogens. Metabolism of ethanol to acetaldehyde in the brain could be deleterious since it can react with cytoskeletal proteins, forming adducts. In the present study, rats were administered ethanol chronically to evaluate its effect on chlorzoxazone hydroxylation in rat brain regions. Chlorzoxazone hydroxylation in brains from the treated rats was induced in hippocampus and cortex, downregulated in brainstem, and unchanged in Cerebellum, striatum, and thalamus. The presence of functionally active P4502E was also seen in human brain regions obtained at autopsy from traffic accident victims. Northern blot analysis of rat and human brain poly(A)(+) RNA hybridized with cDNA to rat CYP2E1 revealed the constitutive presence of a corresponding transcript in rat and human brain. Localization of CYP2E by fluorescence in situ hybridization demonstrated the constitutive expression of CYP2E preferentially in the neuronal Cells in rat and human brain. CYP2E expression was seen in neurons within the cerebral cortex, Purkinje and Granule Cell layers of Cerebellum, Granule Cell layer of dentate gyrus, and pyramidal neurons of CA1, CA2, and CA3 subfields of hippocampus in both rat and human brain. The present studies demonstrate constitutive expression of P4502E1 in brain, its differential induction in rat brain regions by chronic ethanol treatment, and its topographic distribution in rat and human brain.

Norman D Rosenblum - One of the best experts on this subject based on the ideXlab platform.

  • suppressor of fused controls Cerebellum Granule Cell proliferation by suppressing fgf8 and spatially regulating gli proteins
    Development, 2020
    Co-Authors: Tayyaba Jiwani, Norman D Rosenblum
    Abstract:

    Cerebellar Granule Cell (GC) development relies on precise regulation of Sonic Hedgehog (Shh)-Gli signaling activity, failure of which is associated with motor disorders and medulloblastoma. Mutations in pathway regulator Sufu, which modulates Gli activators and repressors, are linked to cerebellar dysfunction and tumourigenesis. The mechanism by which Sufu calibrates Shh signaling in GCs is un known. Math1-Cre-mediated deletion of Sufu in GC progenitors (GCPs) demonstrated that Sufu restricts GCP proliferation and promotes Cell cycle exit, by promoting expression of Gli3R and suppressing Gli2 levels. Sufu is also required to promote high threshold of pathway activity in GCPs. Remarkably, central cerebellar lobules are more deleteriously impacted by Sufu deletion, but are less sensitive to downstream genetic manipulations to reduce Gli2 expression or overexpress a Gli3R mimic, compared to anterior lobules. Transcriptome sequencing uncovered new Sufu targets, especially Fgf8, which is upregulated in Sufu-mutant GCPs. We demonstrated that Fgf8 is necessary and sufficient to drive Sufu-mutant GCP proliferation. This study reveals new insights into the spatial and temporal regulation of cerebellar Shh-Gli signalling, while uncovering new targets such as Fgf8.

David R. Hampson - One of the best experts on this subject based on the ideXlab platform.

  • The calcium-sensing receptor and integrins modulate cerebellar Granule Cell precursor differentiation and migration.
    Developmental neurobiology, 2015
    Co-Authors: Sujeenthar Tharmalingam, David R. Hampson
    Abstract:

    In the developing Cerebellum Granule Cell precursors (GCPs) proliferate in the external Granule Cell layer before differentiating and migrating to the inner Granule Cell layer. Aberrant GCP proliferation leads to medulloblastoma, the most prevalent form of childhood brain cancer. Here, we demonstrate that the calcium-sensing receptor (CaSR), a homodimeric G-protein coupled receptor, functions in conjunction with Cell adhesion proteins, the integrins, to enhance GCP migration and Cell homing by promoting GCP differentiation. During the second postnatal week a robust peak in CaSR expression was observed in GCPs; reciprocal immunoprecipitation experiments conducted during this period established that the CaSR and β1 integrins are present together in a macromolecular protein complex. Analysis of Cell-surface proteins demonstrated that activation of the CaSR by positive allosteric modulators promoted plasma membrane expression of β1 integrins via ERK2 and AKT phosphorylation and resulted in increased GCP migration toward an extraCellular matrix protein. The results of in vivo experiments whereby CaSR modulators were injected i.c.v. revealed that CaSR activation promoted radial migration of GCPs by enhancing GCP differentiation, and conversely, a CaSR inhibitor disrupted GCP differentiation and promoted GCP proliferation. Our results demonstrate that an ion-sensing G-protein coupled receptor acts to promote neuronal differentiation and homing during cerebellar maturation. These findings together with those of others also suggest that CaSR/integrin complexes act to transduce extraCellular calcium signals into Cellular movement, and may function in this capacity as a universal Cell migration/homing complex in the developing brain. © 2015 Wiley Periodicals, Inc. Develop Neurobiol, 2015