Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An elevated level of homocysteine (Hcy) in plasma is an independent risk factor for cardiovascular disease and central nervous system disease. Endothelial dysfunction as a result of apoptosis in endothelial cells is involved in the development and progression of these diseases. In this study, we aimed to investigate the effect of autophagy activation by amino acid starvation on Hcy-induced cytotoxicity in bovine aorta endothelial cells (BAECs). Hcy-induced lactate dehydrogenase (LDH) release was promoted by amino acid starvation. In addition, Hcy increased cleaved caspase-3 level, an indicator of apoptosis, by amino acid starvation. We revealed that oxidative stress is not involved in the Hcy-induced cytotoxicity promoted by amino acid starvation. Salazosulfapyridine (SASP), an SLC7A11 inhibitor, protected against the Hcy-induced LDH release promoted by amino acid starvation. SASP decreased the Hcy-induced cleaved caspase-3 level by amino acid starvation. We demonstrate for the first time that autophagy activation by amino acid starvation promotes Hcy-induced apoptosis in BAECs. Moreover, SLC7A11 inhibitor SASP, which is an amino acid transporter, protects against Hcy-induced apoptosis due to autophagy.
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PMID:Autophagy activation is required for homocysteine-induced apoptosis in bovine aorta endothelial cells. 3202 43

Autophagy is a mechanism that enables cells to maintain cellular homeostasis by removing damaged materials and mobilizing energy reserves in conditions of starvation. Although nutrient availability strongly impacts the process of autophagy, the specific metabolites that regulate autophagic responses have not yet been determined. Recent results indicate that S-adenosylmethionine (SAM) represents a critical inhibitor of methionine starvation-induced autophagy. SAM is primarily involved in four key metabolic pathways: transmethylation, transsulphuration, polyamine synthesis and 5'-deoxyadenosyl 5'-radical-mediated biochemical transformations. SAM is the sole methyl group donor involved in the methylation of DNA, RNA and histones, modulating the autophagic process by mediating epigenetic effects. Moreover, the metabolites of SAM, such as homocysteine, glutathione, decarboxylated SAM and spermidine, also exert important influences on the regulation of autophagy. From our perspective, nuclear-cytosolic SAM is a conserved metabolic inhibitor that connects cellular metabolic status and the regulation of autophagy. In the future, SAM might be a new target of autophagy regulators and be widely used in the treatment of various diseases.
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PMID:S-adenosylmethionine: A metabolite critical to the regulation of autophagy. 3303 Jul 64


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