Lysosomal membrane stabilization by α-tocopherol against the damaging action of Vipera russelli venom phospholipase A2

Mukherjee, Ashis K.; Ghosal, S. K.; Maity, Chiranjit

doi:10.1007/pl00000586

Cited by 40 publications

(17 citation statements)

References 16 publications

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“…These results are suggestive of siramesine-induced lipid peroxidation, because tocopherols, due to their lipophilic nature, are especially effective in protecting lipids from oxidation. It should, however, be noted that in addition to its function as an antioxidant, a-tocopherol has also been reported to inhibit protein kinase C and phospholipase A2, both possible mediators of cell death (36,37).…”

Section: Discussionmentioning

confidence: 99%

Effective Tumor Cell Death by σ-2 Receptor Ligand Siramesine Involves Lysosomal Leakage and Oxidative Stress

et al. 2005

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Acquired resistance to classic caspase-mediated apoptosis is a common problem for the treatment of human cancer. Here, we show that siramesine, a novel S-2 receptor ligand, effectively induces caspase-independent programmed cell death in immortalized and transformed cells of various origins. Siramesine-treated tumor cells displayed increased levels of reactive oxygen species, lysosomal membrane permeabilization, chromatin condensation, and shrinkage and detachment of cells. Lipid antioxidants (A-tocopherol and ;-tocopherol), but not other tested antioxidants (butylated hydroxyanisol or N-acetyl cysteine), effectively inhibited siramesine-induced morphologic changes and cell death. Cathepsin B inhibitors (CA-074-Me and R-2525) conferred similar, but less pronounced protection, whereas ectopic expression of antiapoptotic protein Bcl-2, lack of wild-type p53 as well as pharmacologic inhibitors of caspases (zVADfmk, DEVD-CHO, and LEHD-CHO), calpains (PD150606), and serine proteases (N-tosyl-L-phenylalanine chloromethyl ketone and pefabloc) failed to protect cells against siramesineinduced death. Importantly, transformation of murine embryonic fibroblasts with activated c-src or v-Ha-ras oncogenes greatly sensitized them to siramesine-induced cytotoxicity. Furthermore, p.o. administration of well-tolerated doses of siramesine had a significant antitumorigenic effect in orthotopic breast cancer and s.c. fibrosarcoma models in mice. These results present siramesine as a promising new drug for the treatment of tumors resistant to traditional therapies. (Cancer Res 2005; 65(19): 8975-83)

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Section: Discussionmentioning

confidence: 99%

Effective Tumor Cell Death by σ-2 Receptor Ligand Siramesine Involves Lysosomal Leakage and Oxidative Stress

et al. 2005

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“…TCDD was reported to disturb cell homeostasis, caused cell swelling and cell rupture (Pathak and Kundu, 2013 a, b). Similarly, intracellular increase in ions can elevate the prerequisite CPLA 2 , which is responsible for plasma and lysosomal destabilization (Mukherjee et al 1997). Further, it was reported that intracel-lular ions are able to increase intra-lysosomal pH, probably by interacting with membrane proton pump of the cell .…”

Section: Figmentioning

confidence: 99%

Low Concentration of a Dioxin (2, 3, 7, 8 TCDD) Affects the Glycosidases and Acid Phosphatase Activity in Mice Hepatocytes

Jigyasi

Kundu

2014

Dose-Response

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h Present communication reports the effects of environmentally available, low doses of tetra chloro di benzo-p-dioxin (2,3,7,8 TCDD) to lysosomal enzymes in mice liver. The study tests the hypothesis, in vivo exposure of low dose TCDD provokes dose and duration dependent toxic effects to key lysosomal enzymes and thereby causes cellular apoptotic changes. Three groups of female Swiss albino mice were subjected to two doses of TCDD (0.004 mg/kg bw/d, 0.04 mg/kg bw/d) for 2, 4 and 6 days of exposure durations. The results indicated significant exposure duration dependent effects of TCDD in mice liver cells. The results suggested that TCDD possibly induced an increase in intracellular ions or ROS which in turn altered different physiological activities by affecting different metabolic pathway of the liver cells. The altered functions of key lysosomal enzymes by TCDD may also evoke the process of cellular apoptosis.

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“…It has been suggested that the biochemical properties of PLA 2 enzymes, the availability of PC in a PLA 2 -sensitive membrane and/or various physicochemical properties of a cell membrane are the major factors that show the venom PLA 2 -induced membrane damage [7,9,25,47].…”

Section: Kinetic Parametersmentioning

confidence: 99%

Anticoagulant mechanism and platelet deaggregation property of a non-cytotoxic, acidic phospholipase A2 purified from Indian cobra (Naja naja) venom: Inhibition of anticoagulant activity by low molecular weight heparin

2015

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Lysosomal membrane stabilization by α-tocopherol against the damaging action of Vipera russelli venom phospholipase A2

Cited by 40 publications

References 16 publications

Effective Tumor Cell Death by σ-2 Receptor Ligand Siramesine Involves Lysosomal Leakage and Oxidative Stress

Effective Tumor Cell Death by σ-2 Receptor Ligand Siramesine Involves Lysosomal Leakage and Oxidative Stress

Low Concentration of a Dioxin (2, 3, 7, 8 TCDD) Affects the Glycosidases and Acid Phosphatase Activity in Mice Hepatocytes

Anticoagulant mechanism and platelet deaggregation property of a non-cytotoxic, acidic phospholipase A2 purified from Indian cobra (Naja naja) venom: Inhibition of anticoagulant activity by low molecular weight heparin

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