title: Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat.
abstract: Prolonged ischemia amplified iscehemia/reperfusion (IR) induced renal apoptosis and autophagy. We hypothesize that ischemic conditioning (IC) by a briefly intermittent reperfusion during a prolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated the antioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar rats subjected to sham control, 4 stages of 15-min IC (I15 x 4), 2 stages of 30-min IC (I30 x 2), and total 60-min ischema (I60) in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay, monitoring O2-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hours of reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS) level and proapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome C release, active caspase 3, poly-(ADP-ribose)-polymerase (PARP) degradation fragments, microtubule-associated protein light chain 3 (LC3) and Beclin-1 expression and subsequently tubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level. I30 x 2, not I15 x 4 decreased ROS production and cytochrome C release, increased Manganese superoxide dismutase (MnSOD), Copper-Zn superoxide dismutase (CuZnSOD) and catalase expression and provided a more efficient protection than I60 against IR induced tubular apoptosis and autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renal ischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys. Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content, increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renal tubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in rat kidneys.
authors.affiliation: Department of Medicine, Kuang-Tien General Hospital, Taichung, Taiwan. glory.wu@msa.hinet.net
authors.forename: Hsing-Hui
authors.initials: HH
authors.lastname: Wu
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Hsiao
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
authors.forename: Ming-Kuen
authors.initials: MK
authors.lastname: Lai
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D019194:Ischemic Preconditioning; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D019255:NADPH Oxidases / Q000378:metabolism; D009392:Nephrectomy; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D003404:Creatinine; D009195:Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C027576:4-hydroxy-2-nonenal