Differential patterns of peroxynitrite mediated apoptosis in proximal tubular epithelial cells following ATP depletion recovery. Apoptosis 2008 May;13(5):621-33
Date
03/22/2008Pubmed ID
18357533Pubmed Central ID
PMC2574234DOI
10.1007/s10495-008-0196-7Scopus ID
2-s2.0-42149151520 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Ischemia-reperfusion injury (IRI) is characterized by ATP depletion in the ischemic phase, followed by a rapid increase in reactive oxygen species, including peroxynitrite in the reperfusion phase. In this study, we examined the role of peroxynitrite on cytotoxicity and apoptosis in an in vitro model of ATP depletion-recovery. Porcine proximal tubular epithelial (LLC-PK(1)) cells were ATP depleted for either 2 h (2/2) or 4 h (4/2) followed by recovery in serum free medium for 2 h. A subset of cells was treated with 100 microM of the peroxynitrite scavenger, iron (III) tetrakis (N-methyl-4'pyridyl) porphyrin pentachloride (FeTMPyP) 30 min prior to and during treatment/recovery. Treatment with FeTMPyP reduced cytotoxicity and superoxide levels at both the 2/2 and 4/2 time points, however FeTMPyP decreased nitric oxide only at the 2/2 time point. FeTMPyP also partially blocked caspase-3 and caspase-8 activation at both 2/2 and 4/2 time points. At the 4/2 time point, FeTMPyP also partially inhibited the ATP depletion mediated increase in tumor necrosis factor alpha (TNF-alpha) and decreased Bax and FasL gene expression. These data show that peroxynitrite induces apoptosis by activation of multiple pathways depending on length and severity of insult following ATP depletion-recovery.
Author List
Nilakantan V, Liang H, Maenpaa CJ, Johnson CPAuthor
Christopher P. Johnson MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnimals
Apoptosis
Caspase 3
Caspase Inhibitors
Enzyme Activation
L-Lactate Dehydrogenase
LLC-PK1 Cells
Metalloporphyrins
Mitochondria
Models, Animal
Peroxynitrous Acid
Reperfusion Injury
Swine
Tyrosine