RT Journal Article
SR Electronic
T1 Intracellular GSH Depletion Triggered Mitochondrial Bax Translocation to Accomplish Resveratrol Induced apoptosis in U937 cell Line
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.110.171983
DO 10.1124/jpet.110.171983
A1 Prasun Guha
A1 Anindya Dey
A1 Rupashree Sen
A1 Mitali Chatterjee
A1 Subrata Chattopadhyay
A1 Sandip Kumar Bandyopadhyay
YR 2010
UL http://jpet.aspetjournals.org/content/early/2010/09/27/jpet.110.171983.abstract
AB We have previously demonstrated that Resveratrol induced cellular apoptosis occurs following formation of ROS, but the role of GSH has not been well defined. Our experimental data enumerated that Resv treatment (50µm) induced apoptosis in U937 cell which was preceded by cellular GSH efflux. High concentration of extra cellular thiol (GSH, NAC) and two specific inhibitors of carrier mediated GSH extrusion; methionine or cystathionine prevented the process of oxidative burst and cell death. Thus proved that GSH efflux could be a major molecular switch to modulate Resv induced ROS generation. Spectrofluorimetric data depicted that after 6 h of Resv treatment ROS generation was evident. Pre-treatment of cells with intracellular ROS scavenger (PEG-SOD and PEG-Catalase) efficiently reduced ROS generation but failed to prevent intracellular GSH depletion. Thus, it suggested that intracellular GSH depletion was independent of ROS production but dependent on GSH extrusion. Furthermore, to bridge the link between GSH efflux and ROS generation we carried out confocal microscopy of the localization of Bax protein. Microscopic analysis and siRNA treatment emphasized that cellular GSH efflux triggered Bax translocation to mitochondria which resulted in the loss of mitochondrial membrane potential, ROS generation and caspase 3 activation thus triggered apoptosis.