title: The age-associated loss of ischemic preconditioning in the kidney is accompanied by mitochondrial dysfunction, increased protein acetylation and decreased autophagy.
abstract: In young rats, ischemic preconditioning (IPC), which consists of 4 cycles of ischemia and reperfusion alleviated kidney injury caused by 40-min ischemia. However,old rats lost their ability to protect the ischemic kidney by IPC. A similar aged phenotype was demonstrated in 6-month-old OXYS rats having signs of premature aging. In the kidney of old and OXYS rats, the levels of acetylated nuclear proteins were higher than in young rats, however, unlike in young rats, acetylation levels in old and OXYS rats were further increased after IPC. In contrast to Wistar rats, age-matched OXYS demonstrated no increase in lysosome abundance and LC3 content in the kidney after ischemia/reperfusion. The kidney LC3 levels were also lower in OXYS, even under basal conditions, and mitochondrial PINK1 and ubiquitin levels were higher, suggesting impaired mitophagy. The kidney mitochondria from old rats contained a population with diminished membrane potential and this fraction was expanded by IPC. Apparently, oxidative changes with aging result in the appearance of malfunctioning renal mitochondria due to a low efficiency of autophagy. Elevated protein acetylation might be a hallmark of aging which is associated with a decreased autophagy, accumulation of dysfunctional mitochondria, and loss of protection against ischemia by IPC.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia.
authors.forename: Stanislovas S
authors.initials: SS
authors.lastname: Jankauskas
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia.
authors.forename: Irina B
authors.initials: IB
authors.lastname: Pevzner
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia.
authors.forename: Nadezda V
authors.initials: NV
authors.lastname: Andrianova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia.|International Laser Center, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 62, Moscow, Russia.
authors.forename: Ljubava D
authors.initials: LD
authors.lastname: Zorova
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 73, Moscow, Russia.
authors.forename: Vasily A
authors.initials: VA
authors.lastname: Popkov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia.
authors.forename: Denis N
authors.initials: DN
authors.lastname: Silachev
authors.affiliation: Institute of Cytology and Genetics, Novosibirsk, Russia.
authors.forename: Nataliya G
authors.initials: NG
authors.lastname: Kolosova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia.
authors.forename: Egor Y
authors.initials: EY
authors.lastname: Plotnikov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia.
authors.forename: Dmitry B
authors.initials: DB
authors.lastname: Zorov
mesh_terms: D000107:Acetylation; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000235:genetics; D006801:Humans; D019194:Ischemic Preconditioning; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
chemical_list: D008869:Microtubule-Associated Proteins; C526109:Anxa3 protein, rat