PARP-1 inhibits glycolysis in ischemic kidneys

Kishor Devalaraja-Narashimha, Babu J. Padanilam

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

After ischemic renal injury (IRI), selective damage occurs in the S 3 segments of the proximal tubules as a result of inhibition of glycolysis, but the mechanism of this inhibition is unknown. We previously reported that inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) activity protects against ischemia-induced necrosis in proximal tubules by preserving ATP levels. Here, we tested whether PARP-1 activation in proximal tubules after IRI leads to poly(ADP-ribosyl)ation of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a modification that inhibits its activity. Using in vitro and in vivo models, under hypoxic conditions, we detected poly(ADP-ribosyl)-ation and reduced activity of GAPDH; inhibition of PARP-1 activity restored GAPDH activity and ATP levels. Inhibition of GAPDH with iodoacetate exacerbated ATP depletion, cytotoxicity, and necrotic cell death of LLCPK1 cells subjected to hypoxic conditions, whereas inhibition of PARP-1 activity was cytoprotective. In conclusion, these data indicate that poly(ADP-ribosyl)ation of GAPDH and the subsequent inhibition of anaerobic respiration exacerbate ATP depletion selectively in the proximal tubule after IRI.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalJournal of the American Society of Nephrology
Volume20
Issue number1
DOIs
StatePublished - Jan 2009

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'PARP-1 inhibits glycolysis in ischemic kidneys'. Together they form a unique fingerprint.

Cite this