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)

Glucosylation of RhoA, Rac1, and Cdc42 by Clostridium difficile toxin B from strain VPI 10463 (TcdB) results in actin reorganization (cytopathic effect) and apoptosis (cytotoxic effect). Toxin B from variant C. difficile strain 1470 serotype F (TcdBF) differs from TcdB with regard to substrate proteins, as it glucosylates Rac1 and R-Ras but not RhoA and Cdc42. In this study, we addressed the question of whether the cellular effects of the toxins depend on their protein substrate specificity. Rat basophilic leukemia (RBL) cells were synchronized using the thymidine double-block technique. We show that cells were most sensitive to the cytotoxic effect of TcdB in S phase, as analyzed in terms of phosphatidyl serine externalization, fragmentation of nuclei, and activation of caspase-3; in contrast, TcdBF induced only a marginal cytotoxic effect, suggesting that inactivation of RhoA (but not of Rac1) was required for the cytotoxic effect. The glucosylation of Rac1 was correlated to the cytopathic effect of either toxin, suggesting a close connection of the two effects. The cytotoxic effect of TcdB was executed by caspase-3, as it was responsive to inhibition by acetyl-Asp-Met-Gln-Asp-aldehyde (Ac-DMQD-CHO), an inhibitor of caspase-3. The viability of TcdB-treated RBL cells was reduced, whereas the viability of TcdBF-treated cells was unchanged, further confirming that inactivation of RhoA is required for the cytotoxic effect. In conclusion, the protein substrate specificity of the glucosylating toxins determines their biological activity.
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PMID:Difference in the cytotoxic effects of toxin B from Clostridium difficile strain VPI 10463 and toxin B from variant Clostridium difficile strain 1470. 1714 47

The objective of this work was to find out how the method to extract proteins and subsequent enzymatic hydrolysis affect the ability of hepatic cells to resist oxidative stress. Proteins were isolated from oat brans in the presence of Cellulase (CPI) or Viscozyme (VPI). Four protein hydrolysates were produced from CPI and four others from VPI when they treated with Alcalase, Flavourzyme, Papain, or Protamex. Apart from CPI-Papain that reduced the viability of cell by 20%, no other hydrolysate was cytotoxic in the hepatic HepG2 cells. In the cytoprotection test, VPI-Papain and VPI-Flavourzyme fully prevented the damage due to peroxyl radical while CPI-Papain and CPI-Alcalase enhanced the cellular damage. Cells treated with VPI-hydrolysates reduced intracellular reactive oxygen species (ROS) by 20-40% and, also increased the intracellular concentration of glutathione, compared to CPI-hydrolysates. In antioxidant enzyme assays, although all hydrolysates enhanced the activity of both superoxide dismutase and catalase by up to 2- and 3.4-fold, respectively relative the control cells, the largest increase was due to VPI-Papain and VPI-Flavourzyme hydrolysates. In caspase-3 assays, hydrolysates with reduced ROS or enhanced antioxidant enzyme activities were able to reduce the activity of the pro-apoptotic enzyme, caspase-3 indicating that they prevented oxidative stress-induced cell death.
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PMID:Antioxidant and Anti-Apoptotic Properties of Oat Bran Protein Hydrolysates in Stressed Hepatic Cells. 3108 57