Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic mellitus (DM) portends poor prognosis concerning pressure overloaded heart disease. Branched-chain amino acids (BCAAs), elements of essential amino acids, have been found altered in its catabolism in diabetes decades ago. However, the relationship between BCAAs and DM induced deterioration of pressure overloaded heart disease remains controversial. This study is aimed to investigate the particular effect of BCKA, a metabolite of BCAA, on myocardial injury induced by pressure overloaded. Primary cardiomyocytes were incubated with or without BCKA and followed by treatment with isoproterenol (ISO); then cell viability was detected by CCK8 and apoptosis was examined by TUNNEL stain and caspase-3 activity analysis. Compared to non-BCKA incubated group, BCKA incubation decreased cell survival and increased apoptosis concentration dependently. Furthermore, Western blot assay showed that mTORC2-Akt pathway was significantly inactivated by BCKA incubation. Moreover, overexpression of rictor, a vital component of mTORC2, significantly abolished the adverse effects of BCKA on apoptosis susceptibility of cardiomyocytes. These results indicate that BCKA contribute to vulnerability of cardiomyocytes in stimulated stress via inactivation of mTORC2-Akt pathway.
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PMID:BCKA down-regulates mTORC2-Akt signal and enhances apoptosis susceptibility in cardiomyocytes. 2769 26

Neurodegeneration in diabetic retina has been widely considered as initiating factor that may lead to vascular damage, the classical hallmark of diabetic retinopathy. Diabetes induced altered glutamate metabolism in the retina, especially through glutamate excitotoxicity might play a major role in the neurodegeneration. Increased level of branched chain amino acids (BCAAs) measured in diabetic retina might cause an increase in the neurotoxic level of glutamate by transamination of citric acid cycle intermediates. In order to analyze the transamination of BCAAs and their influence on neurodegenerative factors, we treated streptozotocin-induced diabetic rats with gabapentin, a leucine analogue and an inhibitor of branched chain amino transferase (BCATc). Interestingly, gabapentin lowered the retinal level of BCAAs in diabetic rats. Furthermore, gabapentin treatments ameliorated the reduced antioxidant glutathione level and increased malondialdehyde (MDA), the marker of lipid peroxidation in diabetic rat retinas. In addition, gabapentin also reduced the expression of proapoptotic caspase-3, a marker of apoptosis and increased anti-apoptotic marker Bcl-2 in diabetic retinas. Thus, these results suggest that gabapentin stimulates glutamate disposal, and ameliorates apoptosis and oxidative stress in diabetic rat retina. The influence of gabapentin may be due to its capacity to increase the ratio of BCKA to BCAA which in turn would reduce glutamate excitotoxicity in diabetic retina.
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PMID:Gabapentin Attenuates Oxidative Stress and Apoptosis in the Diabetic Rat Retina. 3083 Jun 78