Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the effect of the calcium- and phospholipid-dependent protein kinase C (PKC) activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the plasma glucose responses to central thyrotropin-releasing hormone (TRH) injection in mice in order to evaluate the involvement of PKC in the mechanism of TRH action in the central nervous system (CNS). TRH (0.1-10 micrograms), as well as the neuroactive TRH analogs, CG 3509, CG 3703, DN 1417, RX 77368, [Nva2]-TRH, KPC-TRH, and TRH-Gly (0.1-10 micrograms), injected centrally in normoglycemic mice reduced the circulating glucose levels in a dose-dependent manner. TPA (0.1-1 microgram), administered centrally together with TRH (1 microgram) or the TRH analogs strongly enhanced the hypoglycemic response. Similar doses of TPA had no effect on plasma glucose when administered alone or together with TRH analogs devoid of central hypoglycemic action, i.e. [Glu1]-TRH, [Phe2]-TRH, and [Gly3]-TRH (1 microgram). Central injection of a TPA analog lacking PKC-stimulating activity, 4-alpha-phorbol (0.1-1 microgram) had no effect on the hypoglycemic response to coadministered TRH. These results, demonstrating a specific effect of TPA in enhancing the hypoglycemic response to central TRH or its neuroactive, though not inactive, analogs are consistent with a possible role for PKC in the mechanism of TRH action in the CNS.
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PMID:TPA (12-O-tetradecanoylphorbol-13-acetate) enhances the central hypoglycemic action of thyrotropin-releasing hormone in mice. 313 16

The manifestation of Lewy bodies (LB) in the brain is a hallmark of Parkinson's disease. Here, we present a comprehensive analysis of protein elements in Lewy bodies by comparative mass spectrometry. Cortical LB inclusions were enriched by sucrose gradient centrifugation from postmortem brains, and a negative control sample was prepared from specimen without LB pathology. Whereas approximately 550 proteins were identified in the LB-enriched sample by mass spectrometry, quantitative comparison with the control sample revealed that approximately 40 proteins were co-enriched with alpha-synuclein, the major component in Lewy bodies. As expected, the list of proteins included previously reported constituents, such as those involved in protein folding, membrane trafficking and oxidative stress. More interestingly, we discovered in the LB-enriched sample several kinases (MAPKK1/MEK1, protein kinase C, and doublecortin-like kinase), a novel deubiquitinating enzyme (otubain 1), and numerous ubiquitin ligases (KPC and SCF). The proteomic studies provide enzyme candidates to investigate the regulation of alpha-synuclein and/or other LB proteins, which may contribute to the formation of Lewy bodies and the toxicity of alpha-synuclein in the related neurodegenerative disorders.
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PMID:Proteomic identification of novel proteins associated with Lewy bodies. 1850 79

The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.
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PMID:Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets. 2510 42