RRC ID 69597
Author Nishi H, Inagi R, Kawada N, Yoshizato K, Mimura I, Fujita T, Nangaku M.
Title Cytoglobin, a novel member of the globin family, protects kidney fibroblasts against oxidative stress under ischemic conditions.
Journal Am J Pathol
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.
Volume 178(1)
Pages 128-39
Published 2011-1-1
DOI 10.1016/j.ajpath.2010.11.011
PII S0002-9440(10)00057-X
PMID 21224051
PMC PMC3069879
MeSH Amino Acid Sequence Animals Base Sequence Cytoglobin Fibroblasts / drug effects Fibroblasts / metabolism Gene Knockdown Techniques Globins / antagonists & inhibitors Globins / genetics Globins / physiology* Heme / antagonists & inhibitors Heme / metabolism Ischemia / genetics Ischemia / metabolism* Ischemia / pathology Kidney / blood supply* Kidney / drug effects Kidney / pathology Molecular Sequence Data Oxidative Stress* Potassium Cyanide / pharmacology Rats Rats, Transgenic Reperfusion Injury / genetics Reperfusion Injury / metabolism* Reperfusion Injury / pathology
IF 3.491
Human and Animal Cells NRK49F(RCB0112)