Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.2 (PDK1)
 2,238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In L6 skeletal muscle cells and immortalized hepatocytes, insulin induced a 2-fold increase in the activity of the pyruvate dehydrogenase (PDH) complex. This effect was almost completely blocked by the protein kinase C (PKC) delta inhibitor Rottlerin and by PKCdelta antisense oligonucleotides. At variance, overexpression of wild-type PKCdelta or of an active PKCdelta mutant induced PDH complex activity in both L6 and liver cells. Insulin stimulation of the activity of the PDH complex was accompanied by a 2.5-fold increase in PDH phosphatases 1 and 2 (PDP1/2) activity with no change in the activity of PDH kinase. PKCdelta antisense blocked insulin activation of PDP1/2, the same as with PDH. In insulin-exposed cells, PDP1/2 activation was paralleled by activation and mitochondrial translocation of PKCdelta, as revealed by cell subfractionation and confocal microscopy studies. The mitochondrial translocation of PKCdelta, like its activation, was prevented by Rottlerin. In extracts from insulin-stimulated cells, PKCdelta co-precipitated with PDP1/2. PKCdelta also bound to PDP1/2 in overlay blots, suggesting that direct PKCdelta-PDP interaction may occur in vivo as well. In intact cells, insulin exposure determined PDP1/2 phosphorylation, which was specifically prevented by PKCdelta antisense. PKCdelta also phosphorylated PDP in vitro, followed by PDP1/2 activation. Thus, in muscle and liver cells, insulin causes activation and mitochondrial translocation of PKCdelta, accompanied by PDP phosphorylation and activation. These events are necessary for insulin activation of the PDH complex in these cells.
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PMID:Activation and mitochondrial translocation of protein kinase Cdelta are necessary for insulin stimulation of pyruvate dehydrogenase complex activity in muscle and liver cells. 1157 86

BACKGROUND Alzheimer's disease (AD) is an age-associated neurodegenerative disorder. This study aimed to investigate effects of acupuncture administration on cognitive function and associated mechanisms. MATERIAL AND METHODS Senescence-accelerated prone 8 (SAM-P8) mice were randomly divided into 3 groups: the SAM-P8 group (P8-CN), the SAM-P8 administrating with acupuncture (P8-Acup) group, and the SAM-P8 administrating without acupuncture (P8-Sham) group. Morris water maze test was conducted to evaluate cognitive functions (memory and learning ability). PDK1, nPKC, and Rac1 inhibitors were used to treat SAM-P8 mice. Transmission electron microscope analysis was used to examine nuclear damage hippocampal tissues. Hematoxylin and eosin (H&E) staining was employed to evaluate inflammation. Western blot was used to detect PI3K, PDK1, nPKC, and Rac 1 expression in hippocampal tissues. RESULTS Acupuncture administration significantly reduced PI3K, PDK1, nPKC, and Rac 1 levels compared to P8-CN group (P<0.05). Both acupuncture and enzyme inhibitors (NSC23766, Rottlerin, OSU03012) significantly improved cognitive functions, reduced inflammation, and alleviated nuclear damages of SAM-P8 mice compared to P8-CN group (P<0.05). Acupuncture significantly enhanced effects of inhibitors on inflammation and nuclear damages compared to inhibitor treatment single (P<0.05). Acupuncture significantly enhanced down-regulative effects of OSU03012 on PI3K and PDK1 levels, increased down-regulative effects of Rottlerin on nPKC and Rac 1 levels and enhanced effects of Rottlerin on Rac 1 compared to P8-CN group (P<0.05). CONCLUSIONS Acupuncture administration improved cognitive functions and alleviated inflammatory response and nuclear damage of SAM-P8 mice, by downregulating PI3K/PDK1/nPKC/Rac 1 signaling pathway. This study could provide potential insight for treating cognitive dysfunction and aging of AD patients.
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PMID:Acupuncture Administration Improves Cognitive Functions and Alleviates Inflammation and Nuclear Damage by Regulating Phosphatidylinositol 3 Kinase (PI3K)/Phosphoinositol-Dependent Kinase 1 (PDK1)/Novel Protein Kinase C (nPKC)/Rac 1 Signaling Pathway in Senescence-Accelerated Prone 8 (SAM-P8) Mice. 3115 45