Cobra cardiotoxin-induced cell death in fetal rat cardiomyocytes and cortical neurons: different pathway but similar cell surface target.
Cobra cardiotoxins (CTXs) are basic polypeptides with diverse pharmacological functions that are cytotoxic to many different cell types through both necrotic and apoptotic cell death pathways. In this comparative study of the action of CTX A3 from the Taiwan cobra (Naja atra) on fetal rat cardiomyocytes and cortical neurons, it was shown that CTX A3 induced different patterns of elevation of intracellular Ca2+ concentration ([Ca2+]i), CTX internalization, caspase-3 activity and viability. Application of an anti-sulfatide monoclonal antibody, O4 specific for 3-sulfo-galactose lipid, but not in the control experiments using anti-GM3 monoclonal antibody, reduces CTX-induced [Ca2+]i elevation, CTX internalization and toxicity. Therefore, CTX may target similar sulfo-containing cell surface receptors in both fetal rat cardiomyocytes and cortical neurons, but induce cell death through different pathways specific to each cell type.
Wang
Chia-Hui
CH
Department of Life Sciences and Institute of Bioinformatics and Structural Biology, National Tsinghua University, 30013 Hsinchu, Taiwan.
Monette
Robert
R
Lee
Shao-Chen
SC
Morley
Paul
P
Wu
Wen-guey
WG
D000818:Animals; D000911:Antibodies, Monoclonal; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects; D004179:Cobra Cardiotoxin Proteins / Q000633:toxicity*; D005333:Fetus / Q000187:drug effects*; D013058:Mass Spectrometry; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013624:Taiwan
D000911:Antibodies, Monoclonal; D004179:Cobra Cardiotoxin Proteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D002118:Calcium