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)

Cellular events for neural progenitor cells, such as proliferation and differentiation, are regulated by multiple intrinsic and extrinsic cell signals. Folate plays a central role in central nervous system development, so folate, as an extrinsic signal, may affect neural stem cell (NSC) proliferation and differentiation. In the present study, we investigated the effects of folate deficiency on the cell proliferation, cell apoptosis and homocysteine concentrations in NSCs. NSCs were isolated from fetal rats and identified as NSCs by their expression of immunoreactive nestin. Cell proliferation was quantitated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells were detected and confirmed by flow cytometric analysis. We measured homocysteine concentrations in NSCs by high performance liquid chromatography and detected the expression of caspase-3 by western blot method. Folate deficiency not only decreased cell proliferation, but also increased the apoptotic rate of NSCs as demonstrated by the increased expression of early apoptotic markers such as caspase-3, compared to control group (p<0.05). Furthermore, There was a statistically significant increase in homocysteine concentration during folate deficiency in NSCs (p<0.05). These data suggest that folate affects the cell proliferation, apoptosis and homocysteine generation in NSC cells.
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PMID:Folate deficiency induces neural stem cell apoptosis by increasing homocysteine in vitro. 1959 Jul 2

We investigated the effects and modes of action of the nutritional factor folate on arsenic-induced toxicity in Chang human hepatocytes. Cells were cultured in folate-deficient medium, normal folate medium or folate-supplemented medium for 1h and then co-treated with or without 20-microM sodium arsenite (NaAsO(2)) for 24h. The results showed that folate deficiency significantly aggravated the NaAsO(2)-induced apoptotic progression [evidenced by phosphatidylserine externalization, cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP), collapse of mitochondrial potential, and release of cytochrome c from the mitochondria] and decrease of cell viability. Folate supplementation significantly attenuated all the above mentioned NaAsO(2)-induced effects except phosphatidylserine externalization. The NaAsO(2)-induced generation of intracellular reactive oxygen species and malondialdehyde was aggravated, to some extent, by folate deficiency, but these phenomena were significantly suppressed by folate supplementation. In contrast, NaAsO(2)-induced elevation of reduced glutathione levels was significantly suppressed by folate deficiency, but significantly enhanced by folate supplementation. In addition, folate deficiency significantly decreased the arsenic methylation capacity of the hepatocytes, but had no effects on cellular retention of arsenic. Folate supplementation had no significant effect on cellular retention or methylation of arsenic. These results indicate that folate deficiency aggravates arsenic-induced toxicity and apoptosis, while folate supplementation attenuates these effects. Folate, which plays a role in arsenic metabolism, also exerts its effect on arsenic toxicity at least partly because of its antioxidant property.
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PMID:Effects of folate on arsenic toxicity in Chang human hepatocytes: involvement of folate antioxidant properties. 2018 6

Apoptosis and proliferation play important roles in embryonic development and are required for neural tube closure. The antifolate drug methotrexate (MTX) induces folate dysmetabolism by inhibition of dihydrofolate reductase and causes abnormal apoptosis and proliferation. In this study, we established an animal model of neural tube defects (NTDs) using MTX to investigate the role of apoptosis and proliferation in NTDs caused by folate deficiency. Differential gene expressions were studied by microarray and reverse transcription-polymerase chain reaction in the NTD animal model. Results showed that 30.8% of NTDs were caused by using MTX in treatment regimens. Microarray indicated that 166 genes were significantly different between the control and NTD mice, including four apoptosis-related genes (Endog, Trp53, Casp3, Bax) and three proliferation-related genes (Ptch1, Pla2g4a, Foxg1). Levels of Endog, Trp53, Casp3, Bax (fold change>1.5) were upregulated but Ptch1, Pla2g4a, Foxg1 (fold change<0.67) were downregulated (P<0.05). These results were confirmed by reverse transcription-polymerase chain reaction. TUNEL, immunohistochemical assays and Western blot were further used to detect apoptosis and proliferation in the NTD animal model. It was found that apoptosis in neuroepithelial cells was increased as determined by TUNEL (P<0.05). Expressions of caspase-3 were significantly enhanced (P<0.05) but expressions of phosphohistone H3 were greatly decreased (P<0.05). These results concluded that MTX caused a folate and folate-associated dysmetabolism, and further induced abnormal apoptosis and proliferation, which may play a critical role in the occurrence of NTDs caused by folate deficiency.
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PMID:Role of methotrexate exposure in apoptosis and proliferation during early neurulation. 2383 30