ABSTRACT
Aspergillus funigatus and other pathogenic fungi synthesize a toxic epidithi-odiopiperzine (ETP) metabolite, namely gliotoxin. Gliotoxin commonly react with sulfhydryl groups, and then, forms hydrogen peroxide. These fungal toxins induce apoptotic cell death in various cells. Apoptosis induced by gliotoxin need calcium. Effect of calcium preconditioning was not reported in gliotoxin-induced apoptosis. To examine the effect of protein kinase C (PKC) and calcium which was regulate caspase-3, PKC and calcium preconditioning before gliotoxin treatment, apoptotic agents such as bcl-2 family, caspase-3 and DNA fragmentation in A7r5 cell line from rat smooth muscle cell were studied. These results showed that gliotoxin induces the expression of bad of bcl-2 family, caspase-3 activation and DNA fragmentation in A7r5 cells. Gliotoxin treatment followed by calcium and PKC preconditioning suppress the Bad of bcl-2 family, and inhibited caspase-3 activation, respectively. These results suggest that PKC and calcium preconditioning protect the gliotoxin-induced apoptosis, through the protection of pro-apoptotic bcl-2 family in A7r5 cells.
Subject(s)
Animals , Humans , Rats , Apoptosis , Aspergillus , Calcium , Caspase 3 , Cell Death , Cell Line , DNA Fragmentation , Fungi , Gliotoxin , Hydrogen Peroxide , Muscle, Smooth , Mycotoxins , Myocytes, Smooth Muscle , Protein Kinase CABSTRACT
Paclitaxel (taxol) is known as effective drug inhibition of cell cycle encouraging activity in human ovarian and metastatic breast cancers and malignant melanoma. It is an antimicrotubule agent that is believed to mediate its antineoplastic effects by inducing mitotic arrest followed by apoptosis. The relation between phorbol 12 myristate 13 acetate (PMA), protein kinase C (PKC) activator, and taxol-induced apoptosis is not well understood until now. This study was performed to investigate the effects of PMA on the signal transduction pathways of taxol-induced apoptosis in MCF-7 human breast carcinoma cells. Taxol-induced apoptosis is attenuated by curcumine, JNK inhibitor, and pyrrolidine dithiocarbamate (PDTC), inhibitor of NFkB. Pretreatment with PKC activator (PMA) or protein kinase A (PKA) activators (forskolin and dibutyryl cAMP) inhibited taxol-induced apoptosis in MCF-7 cells. In addition, thapsigargin, a specific inhibitor of endoplasmic reticulum(ER) Ca(2+)-ATPase and CaCl2, also blocked the activation of caspases by taxol. From these results suggest that taxol-induced apoptosis may be mediated via JNK or NFkB pathway and PKC activation.
Subject(s)
Humans , Apoptosis , Breast , Breast Neoplasms , Caspases , Cell Cycle , Curcumin , Cyclic AMP-Dependent Protein Kinases , MCF-7 Cells , Melanoma , Myristic Acid , Paclitaxel , Protein Kinase C , Signal Transduction , ThapsigarginABSTRACT
Nitric oxide (NO) is mainly involved in brain ischemic damage to elucidate the protective mechanism of NO pretreatment on ischemic-induced cytotoxicity. This study was investigated whether NO pretreatment inhibits the increase of iNOS expression by lipopolysaccharide (LPS) combined phorbol 12-myristate 13-acetate (PMA) via regulating NF-kB activation in C6 glial cells. C6 glial cells with LPS and PMA for 72 hours markedly induced NO, but sodium nitroprusside (SNP) (100 nM) pretreatment before exposure of LPS and PMA significantly supressed NO production, iNOS expression and NF-kB activation by LPS and PMA. In addition, LPS and PMA treatment for 72 hours induced severely cell death and LDH release from cell into media in C6 glial cells. However SNP pretreatment before treatment of LPS and PMA significantly protected LPS and PMA induced cytotoxicity. Treatment with LPS and PMA induced caspase 3 activation follewed by chromosomal condensation, and fragmentation of nuclei in C6 glial cells. SNP pretreatment before exposure to LPS and PMA supressed caspase 3 activation and inhibited chromosomal condensation and fragmentation of nuclei. From these above results, it is suggest that the protective effects of SNP pretreatment against LPS and PMA induced cytotoxicity may be mediated by inhibiting the expression of iNOS via regulating NF-kB activation.
Subject(s)
Brain , Caspase 3 , Cell Death , Neuroglia , NF-kappa B , Nitric Oxide , NitroprussideABSTRACT
No abstract available.