title: Cytoglobin, a novel member of the globin family, protects kidney fibroblasts against oxidative stress under ischemic conditions.
abstract: Cytoglobin (Cygb) is a novel member of the vertebrate globin superfamily. Although it is expressed in splanchnic fibroblasts of various organs, details of its function remain unknown. In the present study, kidney ischemia-reperfusion (I/R) increased the number of Cygb-positive cells per area and up-regulated Cygb mRNA and protein expression in kidney cortex tissues. Similarly, hypoxia up-regulated Cygb expression in cultured rat kidney fibroblasts. The biological function of Cygb in vivo was evaluated in Cygb-overexpressing transgenic rats. Renal dysfunction and histologic damage after renal I/R were ameliorated (mean [SE] serum urea nitrogen concentration after I/R injury, 260.6 [44.9] mg/dL in wild-type rats versus 101.0 [36.0] mg/dL in transgenic rats; P < 0.05) in association with improvement of oxidative stress. Primary cultured fibroblasts from Cygb transgenic rat kidney were resistant to exogenous oxidant stimuli, and treatment of immortalized kidney fibroblasts with Cygb-small interfering RNA (siRNA) enhanced cellular oxidant stress and subsequently decreased cell viability (cell count ratio after exposure to hydrogen peroxide, 35.9% [1.6%] in control-siRNA-treated cells versus 25.5% [2.0%] in Cygb-siRNA-treated cells; P < 0.05). Further, chemical or mutant disruption of heme in Cygb impaired its antioxidant properties, which suggests that the heme of Cygb per se possesses a radical scavenging function. These findings show for the first time, to our knowledge, that Cygb serves as a defensive mechanism against oxidative stress both in vitro and in vivo.
authors.affiliation: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishi
authors.forename: Reiko
authors.initials: R
authors.lastname: Inagi
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.forename: Imari
authors.initials: I
authors.lastname: Mimura
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000078842:Cytoglobin; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005914:Globins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006418:Heme / Q000037:antagonists & inhibitors / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D055647:Rats, Transgenic; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C000627268:Cygb protein, rat; D000078842:Cytoglobin; D006418:Heme; D005914:Globins; D011190:Potassium Cyanide