title: The role of myoglobin degradation in nephrotoxicity after rhabdomyolysis.
abstract: The fate of myoglobin in renal cells was explored in an animal model of rhabdomyolysis known as the pathology highly related to oxidative stress resulting in impairment of renal functioning. The working hypothesis was that the proper degradation of myoglobin in rhabdomyolytic kidney can activate the reparative processes in the tissue. We found that incubation of myoglobin with kidney cells causes its accumulation in the cytoplasm. In rhabdomyolytic rats, the level of heme and free iron in cytoplasm and mitochondria of kidney cells is remarkably increased while inhibition of proteolysis results in further elevation of myoglobin content in the renal tissue. Heme oxygenase and ferritin levels were found to be increased in the kidney tissue at rhabdomyolysis and simulating conditions performed by i/v injection of myoglobin. In addition, the level of peroxidized lipids was high in rhabdomyolytic kidney and became even higher after inhibition of proteolysis by aprotinin. Elevated levels of carbonylated proteins were also observed after rhabdomyolysis, however, if prior to induction of rhabdomyolysis the injection of myoglobin was done, the level of carbonylated proteins dropped versus unprimed kidney tissue thus affording protection to the kidney against oxidative stress. Injection of myoglobin to the rat results in impairment of renal functioning and inhibition of myoglobin degradation in the rhabdomyolytic animal aggravates acute renal failure, demonstrating that degradation of myoglobin is somehow beneficial although it may result in undesired release of free iron which can participate in toxic redox cycling.
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: 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: Anastasia A
authors.initials: AA
authors.lastname: Chupyrkina
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 73, Moscow, Russia.
authors.forename: Savva D
authors.initials: SD
authors.lastname: Zorov
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: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia. Electronic address: plotnikov@genebee.msu.ru.
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. Electronic address: zorov@genebee.msu.su.
authors.forename: Dmitry B
authors.initials: DB
authors.lastname: Zorov
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D005293:Ferritins / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006736:Horses; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009211:Myoglobin / Q000378:metabolism*; D018384:Oxidative Stress; D059748:Proteolysis; D051381:Rats; D012206:Rhabdomyolysis / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D009211:Myoglobin; D006418:Heme; D005293:Ferritins; D006419:Heme Oxygenase (Decyclizing)
keywords: Crush syndrome; Iron; Mitochondria; Myoglobin; Oxidative stress; Peroxidation