The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform

Gary E Gibson - One of the best experts on this subject based on the ideXlab platform.

  • Selective linkage of Mitochondrial Enzymes to intracellular calcium stores differs between human-induced pluripotent stem cells, neural stem cells, and neurons.
    Journal of neurochemistry, 2020
    Co-Authors: Huanlian Chen, Travis T Denton, Abigail C Cross, Ankita Thakkar, Dan Paull, Scott Noggle, Laken Kruger, Gary E Gibson
    Abstract:

    Mitochondria and releasable endoplasmic reticulum (ER) calcium modulate neuronal calcium signaling, and both change in Alzheimer's disease (AD). The releasable calcium stores in the ER are exaggerated in fibroblasts from AD patients and in multiple models of AD. The activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key Mitochondrial Enzyme complex, is diminished in brains from AD patients, and can be plausibly linked to plaques and tangles. Our previous studies in cell lines and mouse neurons demonstrate that reductions in KGDHC increase the ER releasable calcium stores. The goal of these studies was to test whether the relationship was true in human iPSC-derived neurons. Inhibition of KGDHC for one or 24 hr increased the ER releasable calcium store in human neurons by 69% and 144%, respectively. The effect was Mitochondrial Enzyme specific because inhibiting the pyruvate dehydrogenase complex, another key Mitochondrial Enzyme complex, diminished the ER releasable calcium stores. The link of KGDHC to ER releasable calcium stores was cell type specific as the interaction was not present in iPSC or neural stem cells. Thus, these studies in human neurons verify a link between KGDHC and releasable ER calcium stores, and support the use of human neurons to examine mechanisms and potential therapies for AD.

  • reductions in the Mitochondrial Enzyme α ketoglutarate dehydrogenase complex in neurodegenerative disease beneficial or detrimental
    Journal of Neurochemistry, 2016
    Co-Authors: Huanlian Chen, Travis T Denton, Noel Y Calingasan, Flint M Beal, Gary E Gibson
    Abstract:

    Reductions in metabolism and excess oxidative stress are prevalent in multiple neurodegenerative diseases. The activity of the Mitochondrial Enzyme α-ketoglutarate dehydrogenase complex (KGDHC) appears central to these abnormalities. KGDHC is diminished in multiple neurodegenerative diseases. KGDHC can not only be rate limiting for NADH production and for substrate level phosphorylation, but is also a source of reactive oxygen species (ROS). The goal of these studies was to determine how changes in KGDHC modify baseline ROS, the ability to buffer ROS, baseline glutathionylation, calcium modulation and cell death in response to external oxidants. In vivo, reducing KGDHC with adeno virus diminished neurogenesis and increased oxidative stress. In vitro, treatments of short duration increased ROS and glutathionylation and enhanced the ability of the cells to diminish the ROS from added oxidants. However, long-term reductions lessened the ability to diminish ROS, diminished glutathionylation and exaggerated oxidant-induced changes in calcium and cell death. Increasing KGDHC enhanced the ability of the cells to diminish externally added ROS and protected against oxidant-induced changes in calcium and cell death. The results suggest that brief periods of diminished KGDHC are protective, while prolonged reductions are harmful. Furthermore, elevated KGDHC activities are protective. Thus, mitogenic therapies that increase KGDHC may be beneficial in neurodegenerative diseases. Read the Editorial Highlight for this article on Page 689.

  • deficits in the Mitochondrial Enzyme α ketoglutarate dehydrogenase lead to alzheimer s disease like calcium dysregulation
    Neurobiology of Aging, 2012
    Co-Authors: Gary E Gibson, Huanlian Chen, Travis T Denton, Linghua Qiu, Qingli Shi
    Abstract:

    Abstract Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer's disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the Mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K + depolarization that occurs in cells from AD patients and transgenic models of AD. The activity of the Mitochondrial Enzyme KGDHC was diminished acutely (minutes), long-term (days), or chronically (weeks). Acute inhibition of KGDHC produced effects on calcium opposite to those in AD, while the chronic or long-term inhibition of KGDHC mimicked the AD-related changes in calcium. Divergent changes in proteins released from the mitochondria that affect endoplasmic reticulum calcium channels may underlie the selective cellular consequences of acute versus longer term inhibition of KGDHC. The results suggest that the Mitochondrial abnormalities in AD can be upstream of those in calcium.

Huanlian Chen - One of the best experts on this subject based on the ideXlab platform.

  • Selective linkage of Mitochondrial Enzymes to intracellular calcium stores differs between human-induced pluripotent stem cells, neural stem cells, and neurons.
    Journal of neurochemistry, 2020
    Co-Authors: Huanlian Chen, Travis T Denton, Abigail C Cross, Ankita Thakkar, Dan Paull, Scott Noggle, Laken Kruger, Gary E Gibson
    Abstract:

    Mitochondria and releasable endoplasmic reticulum (ER) calcium modulate neuronal calcium signaling, and both change in Alzheimer's disease (AD). The releasable calcium stores in the ER are exaggerated in fibroblasts from AD patients and in multiple models of AD. The activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key Mitochondrial Enzyme complex, is diminished in brains from AD patients, and can be plausibly linked to plaques and tangles. Our previous studies in cell lines and mouse neurons demonstrate that reductions in KGDHC increase the ER releasable calcium stores. The goal of these studies was to test whether the relationship was true in human iPSC-derived neurons. Inhibition of KGDHC for one or 24 hr increased the ER releasable calcium store in human neurons by 69% and 144%, respectively. The effect was Mitochondrial Enzyme specific because inhibiting the pyruvate dehydrogenase complex, another key Mitochondrial Enzyme complex, diminished the ER releasable calcium stores. The link of KGDHC to ER releasable calcium stores was cell type specific as the interaction was not present in iPSC or neural stem cells. Thus, these studies in human neurons verify a link between KGDHC and releasable ER calcium stores, and support the use of human neurons to examine mechanisms and potential therapies for AD.

  • reductions in the Mitochondrial Enzyme α ketoglutarate dehydrogenase complex in neurodegenerative disease beneficial or detrimental
    Journal of Neurochemistry, 2016
    Co-Authors: Huanlian Chen, Travis T Denton, Noel Y Calingasan, Flint M Beal, Gary E Gibson
    Abstract:

    Reductions in metabolism and excess oxidative stress are prevalent in multiple neurodegenerative diseases. The activity of the Mitochondrial Enzyme α-ketoglutarate dehydrogenase complex (KGDHC) appears central to these abnormalities. KGDHC is diminished in multiple neurodegenerative diseases. KGDHC can not only be rate limiting for NADH production and for substrate level phosphorylation, but is also a source of reactive oxygen species (ROS). The goal of these studies was to determine how changes in KGDHC modify baseline ROS, the ability to buffer ROS, baseline glutathionylation, calcium modulation and cell death in response to external oxidants. In vivo, reducing KGDHC with adeno virus diminished neurogenesis and increased oxidative stress. In vitro, treatments of short duration increased ROS and glutathionylation and enhanced the ability of the cells to diminish the ROS from added oxidants. However, long-term reductions lessened the ability to diminish ROS, diminished glutathionylation and exaggerated oxidant-induced changes in calcium and cell death. Increasing KGDHC enhanced the ability of the cells to diminish externally added ROS and protected against oxidant-induced changes in calcium and cell death. The results suggest that brief periods of diminished KGDHC are protective, while prolonged reductions are harmful. Furthermore, elevated KGDHC activities are protective. Thus, mitogenic therapies that increase KGDHC may be beneficial in neurodegenerative diseases. Read the Editorial Highlight for this article on Page 689.

  • deficits in the Mitochondrial Enzyme α ketoglutarate dehydrogenase lead to alzheimer s disease like calcium dysregulation
    Neurobiology of Aging, 2012
    Co-Authors: Gary E Gibson, Huanlian Chen, Travis T Denton, Linghua Qiu, Qingli Shi
    Abstract:

    Abstract Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer's disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the Mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K + depolarization that occurs in cells from AD patients and transgenic models of AD. The activity of the Mitochondrial Enzyme KGDHC was diminished acutely (minutes), long-term (days), or chronically (weeks). Acute inhibition of KGDHC produced effects on calcium opposite to those in AD, while the chronic or long-term inhibition of KGDHC mimicked the AD-related changes in calcium. Divergent changes in proteins released from the mitochondria that affect endoplasmic reticulum calcium channels may underlie the selective cellular consequences of acute versus longer term inhibition of KGDHC. The results suggest that the Mitochondrial abnormalities in AD can be upstream of those in calcium.

W. R. Robertson - One of the best experts on this subject based on the ideXlab platform.

  • The effects of hypo- and hyperthyroidism on fibre composition and Mitochondrial Enzyme activities in rat skeletal muscle.
    The Journal of endocrinology, 1992
    Co-Authors: R. B. Lomax, W. R. Robertson
    Abstract:

    Hypo- and hyperthyroidism have been associated with changes in the activities of Mitochondrial Enzymes in homogenates of skeletal muscles, but it is unclear whether such changes were due to changes in single fibre Enzyme activities or to previously documented changes in relative numbers of fibres. In this study the activities of the Mitochondrial Enzymes alpha-glycerol phosphate dehydrogenase (m-alpha GPDH) and succinate dehydrogenase (SDH) were measured in single fibres of the soleus and gastrocnemius muscles of the rat by cytochemical assays. In the soleus muscles of hypothyroid animals there was a decrease in the mean percentage (+/- S.D.) of type II fibres from 8.0 +/- 6.0 to 0.8 +/- 1.9% (P less than 0.05) and decreases in SDH activities in all fibre types (P less than 0.005). In the gastrocnemius muscles of these animals there were no changes in fibre composition but type IIB fibres had reduced (P less than 0.05) m-alpha GPDH activities. In the hyperthyroid animals, in which body weight had increased relative to the euthyroid animals, there were increases in the percentages of type IC and type II fibres in the soleus from 4.3 +/- 1.7 to 13.1 +/- 9.0% (P less than 0.05) and from 9.6 +/- 7.2 to 33.4 +/- 9.6% (P less than 0.005) respectively and an increase in the percentage of type IIA fibres in the gastrocnemius from 92.9 +/- 2.3 to 97.0 +/- 2.9% (P less than 0.05). However, there were no increases in single fibre Mitochondrial Enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitsuru Higuchi - One of the best experts on this subject based on the ideXlab platform.

  • Alternate-Day High-Fat Diet Induces an Increase in Mitochondrial Enzyme Activities and Protein Content in Rat Skeletal Muscle.
    Nutrients, 2016
    Co-Authors: Kazuhiko Higashida, Takuji Kawamura, Mitsuru Higuchi
    Abstract:

    Long-term high-fat diet increases muscle Mitochondrial Enzyme activity and endurance performance. However, excessive calorie intake causes intra-abdominal fat accumulation and metabolic syndrome. The purpose of this study was to investigate the effect of an alternating day high-fat diet on muscle Mitochondrial Enzyme activities, protein content, and intra-abdominal fat mass in rats. Male Wistar rats were given a standard chow diet (CON), high-fat diet (HFD), or alternate-day high-fat diet (ALT) for 4 weeks. Rats in the ALT group were fed a high-fat diet and standard chow every other day for 4 weeks. After the dietary intervention, Mitochondrial Enzyme activities and protein content in skeletal muscle were measured. Although body weight did not differ among groups, the epididymal fat mass in the HFD group was higher than those of the CON and ALT groups. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities in the plantaris muscle of rats in HFD and ALT were significantly higher than that in CON rats, whereas there was no difference between HFD and ALT groups. No significant difference was observed in muscle glycogen concentration or glucose transporter-4 protein content among the three groups. These results suggest that an alternate-day high-fat diet induces increases in Mitochondrial Enzyme activities and protein content in rat skeletal muscle without intra-abdominal fat accumulation.

Travis T Denton - One of the best experts on this subject based on the ideXlab platform.

  • Selective linkage of Mitochondrial Enzymes to intracellular calcium stores differs between human-induced pluripotent stem cells, neural stem cells, and neurons.
    Journal of neurochemistry, 2020
    Co-Authors: Huanlian Chen, Travis T Denton, Abigail C Cross, Ankita Thakkar, Dan Paull, Scott Noggle, Laken Kruger, Gary E Gibson
    Abstract:

    Mitochondria and releasable endoplasmic reticulum (ER) calcium modulate neuronal calcium signaling, and both change in Alzheimer's disease (AD). The releasable calcium stores in the ER are exaggerated in fibroblasts from AD patients and in multiple models of AD. The activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key Mitochondrial Enzyme complex, is diminished in brains from AD patients, and can be plausibly linked to plaques and tangles. Our previous studies in cell lines and mouse neurons demonstrate that reductions in KGDHC increase the ER releasable calcium stores. The goal of these studies was to test whether the relationship was true in human iPSC-derived neurons. Inhibition of KGDHC for one or 24 hr increased the ER releasable calcium store in human neurons by 69% and 144%, respectively. The effect was Mitochondrial Enzyme specific because inhibiting the pyruvate dehydrogenase complex, another key Mitochondrial Enzyme complex, diminished the ER releasable calcium stores. The link of KGDHC to ER releasable calcium stores was cell type specific as the interaction was not present in iPSC or neural stem cells. Thus, these studies in human neurons verify a link between KGDHC and releasable ER calcium stores, and support the use of human neurons to examine mechanisms and potential therapies for AD.

  • reductions in the Mitochondrial Enzyme α ketoglutarate dehydrogenase complex in neurodegenerative disease beneficial or detrimental
    Journal of Neurochemistry, 2016
    Co-Authors: Huanlian Chen, Travis T Denton, Noel Y Calingasan, Flint M Beal, Gary E Gibson
    Abstract:

    Reductions in metabolism and excess oxidative stress are prevalent in multiple neurodegenerative diseases. The activity of the Mitochondrial Enzyme α-ketoglutarate dehydrogenase complex (KGDHC) appears central to these abnormalities. KGDHC is diminished in multiple neurodegenerative diseases. KGDHC can not only be rate limiting for NADH production and for substrate level phosphorylation, but is also a source of reactive oxygen species (ROS). The goal of these studies was to determine how changes in KGDHC modify baseline ROS, the ability to buffer ROS, baseline glutathionylation, calcium modulation and cell death in response to external oxidants. In vivo, reducing KGDHC with adeno virus diminished neurogenesis and increased oxidative stress. In vitro, treatments of short duration increased ROS and glutathionylation and enhanced the ability of the cells to diminish the ROS from added oxidants. However, long-term reductions lessened the ability to diminish ROS, diminished glutathionylation and exaggerated oxidant-induced changes in calcium and cell death. Increasing KGDHC enhanced the ability of the cells to diminish externally added ROS and protected against oxidant-induced changes in calcium and cell death. The results suggest that brief periods of diminished KGDHC are protective, while prolonged reductions are harmful. Furthermore, elevated KGDHC activities are protective. Thus, mitogenic therapies that increase KGDHC may be beneficial in neurodegenerative diseases. Read the Editorial Highlight for this article on Page 689.

  • deficits in the Mitochondrial Enzyme α ketoglutarate dehydrogenase lead to alzheimer s disease like calcium dysregulation
    Neurobiology of Aging, 2012
    Co-Authors: Gary E Gibson, Huanlian Chen, Travis T Denton, Linghua Qiu, Qingli Shi
    Abstract:

    Abstract Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer's disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the Mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K + depolarization that occurs in cells from AD patients and transgenic models of AD. The activity of the Mitochondrial Enzyme KGDHC was diminished acutely (minutes), long-term (days), or chronically (weeks). Acute inhibition of KGDHC produced effects on calcium opposite to those in AD, while the chronic or long-term inhibition of KGDHC mimicked the AD-related changes in calcium. Divergent changes in proteins released from the mitochondria that affect endoplasmic reticulum calcium channels may underlie the selective cellular consequences of acute versus longer term inhibition of KGDHC. The results suggest that the Mitochondrial abnormalities in AD can be upstream of those in calcium.