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Differential patterns of peroxynitrite mediated apoptosis in proximal tubular epithelial cells following ATP depletion recovery. Apoptosis 2008 May;13(5):621-33

Date

03/22/2008

Pubmed ID

18357533

Pubmed Central ID

PMC2574234

DOI

10.1007/s10495-008-0196-7

Scopus ID

2-s2.0-42149151520   13 Citations

Abstract

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 CP

Author

Christopher P. Johnson MD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Apoptosis
Caspase 3
Caspase Inhibitors
Enzyme Activation
L-Lactate Dehydrogenase
LLC-PK1 Cells
Metalloporphyrins
Mitochondria
Models, Animal
Peroxynitrous Acid
Reperfusion Injury
Swine
Tyrosine
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00