SOD1 and MitoTEMPO partially prevent mitochondrial permeability transition pore opening, necrosis, and mitochondrial apoptosis after ATP depletion recovery. Free Radic Biol Med 2010 Nov 30;49(10):1550-60
Date
08/26/2010Pubmed ID
20736062Pubmed Central ID
PMC3863116DOI
10.1016/j.freeradbiomed.2010.08.018Scopus ID
2-s2.0-77957751549 (requires institutional sign-in at Scopus site) 125 CitationsAbstract
Generation of excessive reactive oxygen species (ROS) leads to mitochondrial dysfunction, apoptosis, and necrosis in renal ischemia-reperfusion (IR) injury. Previously we showed that lentiviral vector-mediated overexpression of superoxide dismutase-1 (SOD1) in proximal tubular epithelial cells (LLC-PK(1)) reduced cytotoxicity in an in vitro model of IR injury. Here, we examined the effects of SOD1 overexpression on mitochondrial signaling after ATP depletion-recovery (ATP-DR). To examine the role of mitochondrial ROS, a subset of cells was treated with the mitochondrial antioxidant MitoTEMPO. ATP-DR-mediated increase in mitochondrial calcium, loss of mitochondrial membrane potential, and increase in mitochondrial permeability transition pore (MPTP) were attenuated by SOD1 and MitoTEMPO (P<0.01). SOD1 prevented ATP-DR-induced mitochondrial Bax translocation, although the release of proapoptotic proteins from mitochondria was not prevented by SOD1 alone and required the presence of both SOD1 and MitoTEMPO. SOD1 suppressed the increase in c-jun phosphorylation, suggesting that JNK signaling regulates Bax translocation to mitochondria via ROS. ATP-DR-mediated changes in MPTP and mitochondrial signaling increased necrosis and apoptosis, both of which were partially attenuated by SOD1 and MitoTEMPO. These studies show that SOD1 and MitoTEMPO preserve mitochondrial integrity and attenuate ATP-DR-mediated necrosis and apoptosis.
Author List
Liang HL, Sedlic F, Bosnjak Z, Nilakantan VMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnimals
Antioxidants
Apoptosis
Cyclic N-Oxides
Mitochondria
Mitochondrial Membrane Transport Proteins
Mitochondrial Proteins
Mitogen-Activated Protein Kinase 8
Necrosis
Organophosphorus Compounds
Phosphorylation
Piperidines
Proto-Oncogene Proteins c-jun
Superoxide Dismutase
Superoxide Dismutase-1
Swine
