Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ochratoxin A (OTA) is a widespread mycotoxin contaminating feed and food. Besides its potent nephrotoxicity, OTA also affects the immune system. We demonstrate here a role for Bcl-x(L) in OTA-induced apoptosis in human lymphocytes. In particular, human peripheral blood lymphocytes and the human lymphoid T cell line, Kit 225 cells, underwent apoptosis in a time- and dose-dependent manner. This apoptosis was inhibited by z-VAD.fmk, suggesting that caspases were responsible for the induction of apoptosis. Moreover, OTA triggered mitochondrial transmembrane potential (Deltachim) loss and caspase-9 and caspase-3 activation. Interestingly, Bcl-x(L) protein expression was decreased by OTA treatment, whereas Bcl-2 protein level was not affected. Down-regulation of bcl-x(L) mRNA was not observed in cells treated with OTA. Overexpression of Bcl-x(L) in Kit 225 cells protected them against mitochondrial perturbation and retarded the appearance of apoptotic cells. Taken together, our data indicate that mitochondria are a central component in OTA-induced apoptosis and that the loss of Bcl-x(L) may participate in OTA-induced cell death.
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PMID:Ochratoxin A induces apoptosis in human lymphocytes through down regulation of Bcl-xL. 1505 5

Ochratoxin A (OTA), a mycotoxin constituent of a range of food commodities, including coffee, wine, beer, grains, and spices, exerts toxicological and pathological effects in vivo, such as nephrotoxicity, hepatotoxicity, and immunotoxicity. In a previous report, we highlighted the potential of OTA to induce apoptosis via reactive oxygen species (ROS) generation in mouse blastocysts that led to impaired preimplantation and postimplantation embryo development in vitro and in vivo. Here, we have shown that liquiritigenin (LQ), a type of flavonoid isolated from Glycyrrhiza radix, effectively protects against OTA-mediated apoptosis and inhibition of cell proliferation in mouse blastocysts. Preincubation of blastocysts with LQ clearly prevented OTA-triggered impairment of preimplantation and postimplantation embryonic development and fetal weight loss, both in vitro and in vivo. Detailed investigation of regulatory mechanisms revealed that OTA mediated apoptosis and embryotoxicity through ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase-9 and caspase-3, which were effectively prevented by LQ. The embryotoxic effects of OTA were further validated in an animal model in vivo. Intravenous injection of dams with OTA (3 mg/kg/day) led to apoptosis of blastocysts, impairment of embryonic development from zygote to blastocyst stage and decrease in day 18 fetal weight. Notably, preinjection of dams with LQ (5 mg/kg/day) effectively prevented OTA-induced apoptosis and toxic effects on embryo development. Our collective results clearly demonstrate that OTA exposure via injection has the potential to damage preimplantation and postimplantation embryonic development against which LQ has a protective effect.
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PMID:Prevention of ochratoxin A-induced oxidative stress-mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin. 3069 92