Changes in protein kinase C isozymes in the rat hippocampus following transient hypoxia

Yamaoka, Yumiko; Shimohama, Shun; Kimura, Jun; Fukunaga, Reiko; Taniguchi, Takashi

doi:10.1016/0304-3940(93)90161-d

Cited by 10 publications

(4 citation statements)

References 17 publications

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“…Therefore, we proposed that hypoxic stress in these cells activates signal transduction pathways, possibly involving calcium influx from an extracellular source, which results in the induction of PKC␥ [Huang et al, 1999]. These results were consistent with those of the others in that cyanide induced PKC translocation [Rathinavelu et al, 1994;Yamaoka et al, 1993], and transient ischemia induces PKC␦ activation [Miettinen et al, 1996]. Cyanideinduced catecholamine release is Ca 2ϩ mediated and is involved in neurotoxicity [Kanthasamy et al, 1991].…”

Section: Discussionsupporting

confidence: 80%

Differential alteration of catecholamine release during chemical hypoxia is correlated with cell toxicity and is blocked by protein kinase C inhibitors in PC12 cells

et al. 2000

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Release of neurotransmitters, including dopamine and glutamate, has been implicated in hypoxia/ischemia-induced alterations in neuronal function and in subsequent tissue damage. Although extensive studies have been done on the mechanism underlying the changes in glutamate release, few have examined the mechanism that is responsible for the changes in catecholamines. Rat pheochromocytoma-12 (PC12) cells synthesize, store, and release catecholamines including DA and NE. Therefore, we used HPLC and ED to evaluate extracellular DA and NE concentrations in a medium during chemical hypoxia in PC12 cells. Chemical hypoxia produced by KCN induced differential release of DA and NE. Under normal glucose conditions, KCN induced release of NE, but not DA. Under glucose-free conditions, KCN-induced release of DA was elevated transiently, whereas the release of NE increased progressively. Under parallel conditions, KCN biphasically elevated the level of cytosolic free calcium ([CA(2+)](i)) in glucose-free DMEM, peaking at 95 +/- 18 nM at 1,107 +/- 151 s, followed by a new plateau level at 249 +/- 24 nM sustained from 4,243 +/- 466 to 5,263 +/- 440 s. Cell toxicity, as measured by LDH release, was increased significantly by KCN in glucose-free DMEM but was diminished in the presence of glucose, and was correlated with DA release by chemical hypoxia. The protein kinase C (PKC) inhibitor GO6976 or staurosporine inhibited KCN-induced LDH release as well as the release of NE and DA. Taken together, selective activation of DA but not NE was correlated with the LDH release by chemical hypoxia, and was diminished with GO6976 or staurosporine. These results suggest that selective activation of PKC isoforms is involved in the chemical hypoxia-induced DA release, which may lead to neuronal cell toxicity.

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Section: Discussionsupporting

confidence: 80%

Differential alteration of catecholamine release during chemical hypoxia is correlated with cell toxicity and is blocked by protein kinase C inhibitors in PC12 cells

et al. 2000

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“…Regulatory pathways involved in the inhibition of K ϩ channels include association with ␤-subunits or phosphorylation by protein kinase C (PKC) (1,3,12,14). Hypoxia alters PKC isozyme expression and subcellular distribution (6,28). Exposure of cultured PASMCs to hypoxia decreases mRNA and protein expression of K V ␣-subunits, whereas K V ␤-subunit expression is unaffected (26).…”

Section: Discussionmentioning

confidence: 99%

Partial HIF-1α deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia

Shimoda

Manalo

Sham

et al. 2001

American Journal of Physiology-Lung Cellular and Molecular Phys

195

146

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Chronic hypoxia depolarizes and reduces K+ current in pulmonary arterial smooth muscle cells (PASMCs). Our laboratory previously demonstrated that hypoxia-inducible factor-1 (HIF-1) contributed to the development of hypoxic pulmonary hypertension. In this study, electrophysiological parameters were measured in PASMCs isolated from intrapulmonary arteries of mice with one null allele at the Hif1a locus encoding HIF-1alpha [Hif1a(+/-)] and from their wild-type [Hif1a(+/+)] littermates after 3 wk in air or 10% O2. Hematocrit and right ventricular wall and left ventricle plus septum weights were measured. Capacitance, K+ current, and membrane potential were measured with whole cell patch clamp. Similar to our laboratory's previous results, hypoxia-induced right ventricular hypertrophy and polycythemia were blunted in Hif1a(+/-) mice. Hypoxia increased PASMC capacitance in Hif1a(+/+) mice but not in Hif1a(+/-) mice. Chronic hypoxia depolarized and reduced K+ current density in PASMCs from Hif1a(+/+) mice. In PASMCs from hypoxic Hif1a(+/-) mice, no reduction in K+ current density was observed, and depolarization was significantly blunted. Thus partial deficiency of HIF-1alpha is sufficient to impair hypoxia-induced depolarization, reduction of K+ current density, and PASMC hypertrophy.

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“…Ca 2-dependent PKC assay was determined by using a commercially available PKC enzyme assay system (Amersham, U.K.) as described previously (Cardell et al, 1991;Yamaoka et al, 1993;Uehara-Kunugi et a!., 1994). In brief, the reaction mixtures (75~l) containing 50 mM Tris-HC1 (pH 7.5), 50~zg/ml PS, 150 ng phorbol 12-myristate 13acetate (PMA), 2.5 mM dithiothreitol, 50~M ATP, 0.25 sCi [y-32P]ATP, 0.5 mM calcium acetate, 15 mM magnesium acetate, 75 mM specific substrate peptide, and a brain extract.…”

Section: Pkc Assaymentioning

confidence: 99%

Ca²⁺‐Dependent and Ca²⁺‐Independent Protein Kinase C Changes in the Brains of Patients with Alzheimer's Disease

Matsushima

Shimohama

Chachin

et al. 1996

Journal of Neurochemistry

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We examined protein kinase C (PKC) activity in Ca2-dependent PKC (Ca2-dependent PKC activities) and Ca2-independent PKC (Ca2-independent PKC activities) assay conditions in brains from Alzheimer's disease (AD) patients and age-matched controls. In cytosolic and membranous fractions, Ca2~-dependent and Ca2-independent PKC activities were significantly lower in AD brain than in control brain. In particular, reduction of Ca2~-independentPKC activity in the membranous fraction of AD brain was most enhanced when cardiolipin, the optimal stimulator of PKC-, was used in the assay; whereas Ca2~-independentPKC activity stimulated by phosphatidylinositol, the optimal stimulator of PKC-6, was not significantly reduced in AD. Further studies on the protein levels of Ca2~-independentPKC-6, PKC-e, and PKC-ĩn AD brain revealed reduction of the PKClevel in both cytosolic and membranous fractions, although PKC-6 and PKC-levels were not changed. These findings indicated that Ca2-dependent and Ca2~-independent PKC are changed in AD, and that among Ca2~independent PKC isozymes, the alteration of PKC-is a specific event in AD brain, suggesting its crucial role in AD pathophysiology. Key Words: Alzheimer's disease-Ca2 -dependent protein kinase C-Ca 2k-independent protein kinase C-Protein kinase C-c-Brain.

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Changes in protein kinase C isozymes in the rat hippocampus following transient hypoxia

Cited by 10 publications

References 17 publications

Differential alteration of catecholamine release during chemical hypoxia is correlated with cell toxicity and is blocked by protein kinase C inhibitors in PC12 cells

Differential alteration of catecholamine release during chemical hypoxia is correlated with cell toxicity and is blocked by protein kinase C inhibitors in PC12 cells

Partial HIF-1α deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia

Ca²⁺‐Dependent and Ca²⁺‐Independent Protein Kinase C Changes in the Brains of Patients with Alzheimer's Disease

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Changes in protein kinase C isozymes in the rat hippocampus following transient hypoxia

Cited by 10 publications

References 17 publications

Differential alteration of catecholamine release during chemical hypoxia is correlated with cell toxicity and is blocked by protein kinase C inhibitors in PC12 cells

Differential alteration of catecholamine release during chemical hypoxia is correlated with cell toxicity and is blocked by protein kinase C inhibitors in PC12 cells

Partial HIF-1α deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia

Ca2+‐Dependent and Ca2+‐Independent Protein Kinase C Changes in the Brains of Patients with Alzheimer's Disease

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Ca²⁺‐Dependent and Ca²⁺‐Independent Protein Kinase C Changes in the Brains of Patients with Alzheimer's Disease