Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 178, Issue 1, Pages 128-139Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2010.11.011
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Funding
- Japan Society for the Promotion of Science [09J07041, 19390228, 2139036, 19590939]
- Ninth Japanese Society for Pathophysiological and Therapeutic Research in Renal Failure
- Ishidsu Shun Memorial Scholarship
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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-over-expressing 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. (Am J Pathol 2011, 178: 128-139; DOI: 10.1016/j.ajpath.2010.11.011)
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