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Regulation of JNK/ERK activation, cell apoptosis, and tissue regeneration by monoamine oxidases after renal ischemia‐reperfusion
Author(s) -
Kunduzova Oxana R.,
Bianchi Pascale,
Pizzinat Nathalie,
Escourrou Ghislaine,
Seguelas MarieHelene,
Parini Angelo,
Cambon Claudie
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-1008fje
Subject(s) - reperfusion injury , renal ischemia , programmed cell death , ischemia , apoptosis , reactive oxygen species , chemistry , mapk/erk pathway , kinase , pharmacology , kidney , microbiology and biotechnology , biology , medicine , endocrinology , biochemistry
ABSTRACT Reactive oxygen species (ROS) contribute to the ischemia‐reperfusion injury. In kidney, the intracellular sources of ROS during ischemia‐reperfusion are still unclear. In the present study, we investigated the role of the catecholamine‐degrading enzyme monoamine oxidases (MAOs) in hydrogen peroxide (H 2 O 2 ) generation after reperfusion and their involvement in cell events leading to tissue injury and recovery. In a rat model of renal ischemia‐reperfusion, we show concomitant MAO‐dependent H 2 O 2 production and lipid peroxidation in the early reperfusion period. Rat pretreatment with the irreversible MAO inhibitor pargyline resulted in the following: i) prevented H 2 O 2 production and lipid peroxidation; ii) decreased tubular cell apoptosis and necrosis, measured by TUNEL staining and histomorphological criteria; and iii) increased tubular cell proliferation as determined by proliferating cell nuclear antigen expression. MAO inhibition also prevented Jun N‐terminal kinase phosphorylation and promoted extracellular signal‐regulated kinase activation, two mitogen‐activated protein kinases described as a part of a “death” and “survival” pathway after ischemia‐reperfusion. This work demonstrates the crucial role of MAOs in mediating the production of injurious ROS, which contribute to acute apoptotic and necrotic cell death induced by renal ischemia‐reperfusion in vivo. Targeted inhibition of these oxidases could provide a new avenue for therapy to prevent renal damage and promote renal recovery after ischemia‐reperfusion.