Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study shows the effects of L-carnitine treatment on cell proliferation with hepa1c1c7 mouse cancer cells and NCTC 1469 normal cells. In an MTT assay, L-carnitine increased the number of dead hepa1c1c7 cells, while there was no difference in the number of NCTC 1469 cells. mRNA and protein levels of TNF-alpha, Fas, and caspase-8, which are closely related to cell apoptosis by a death ligand/receptor-dependent apoptosis pathway, were increased by L-carnitine treatment. In addition, L-carnitine treatment regulated mitochondria-dependent apoptosis pathways by inducing the up-regulation of caspase-9 and caspase-3 and the down-regulation of Bcl-2 in hepa1c1c 7 cells. Taken together, the findings of this study have demonstrated that L-carnitine could induce apoptosis in hepa1c1c7 cells by regulating Fas ligands and inhibiting the expression of Bcl-2. These results suggest that L: -carnitine treatment could be related to both a mitochondrion-dependent and a death ligand/receptor-dependent apoptosis pathway in hepa1c1c7 cells. Our results could give information for understanding the L-carnitine-induced apoptosis mechanism in some cancer cells.
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PMID:Induction of apoptosis by L-carnitine through regulation of two main pathways in Hepa1c1c 7 cells. 1844 97

To elucidate the mechanism by which L-carnitine and related metabolites inhibited mitochondria-dependent apoptosis, we used conditional TRX2-knockout DT40 cells (TRX2(-/-)) and compared the properties of signaling pathways leading to apoptosis in the wild and TRX2(-/-) cells. Caspase-3 and 9, but not caspase-8, were strongly activated in TRX2(-/-) cells but not in wild cells. TRX2(-/-) cells generated large amounts of reactive oxygen species that markedly decreased cellular glutathione levels both in cytosol and mitochondria. We found that the critical thiol groups of adenine nucleotide translocator (ANT) were oxidized more easily in TRX2(-/-) cells than in wild cells and that the reduced form, but not oxidized form, of ANT selectively bound to TRX2. Cytochrome c and SOD1 were released from mitochondria more easily in TRX2(-/-) cells than in wild cells. All these phenomena observed with TRX2(-/-) cells were effectively inhibited by acetyl-L-carntine but not L-carnitine. Thus, acetyl-L-carnitine effectively suppressed the oxidative stress in and around mitochondria thereby preventing mitochondrial signaling pathway leading to apoptosis.
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PMID:Acetyl-L-carnitine suppresses apoptosis of thioredoxin 2-deficient DT40 cells. 1871 18