Effects of glutathione depletion on hypoxia-induced erythropoietin production in rats.
In vitro studies have indicated that reactive oxygen species modifying cellular redox status are involved in hypoxia-induced erythropoietin (EPO) production. However, the effects of redox balance on hypoxia-induced EPO production in vivo are still not fully understood. To investigate the effect of the change in cellular redox status on EPO generation, we determined whether glutathione (GSH) depletion has a significant influence on hypoxia-induced EPO production in rats. For the inhibition of GSH synthesis, DL-buthionine-[S,R]-sulfoximine (BSO) was employed by intraperitoneal injection. Twenty male rats were assigned to one of four experimental groups: (1) normoxic placebo, (2) normoxic BSO, (3) hypoxic placebo, and (4) hypoxic BSO. Hypoxic groups were exposed to a simulated normobaric hypoxic condition (4,500 m above sea level) for 12 hours. BSO treatment resulted in a significant depletion of total GSH levels in kidney and plasma in both conditions. However, the hypoxia-induced elevation in serum EPO concentration was not completely affected by the inhibition of GSH synthesis. These data demonstrate that GSH depletion in the kidney is not involved in the increase in serum EPO concentration in response to systemic hypoxia. It is also conceivable that the cellular redox changes could not function as a primary regulator of hypoxia-induced renal erythropoietin formation in vivo.
Ando
Daisuke
D
Department of Physical Education, National Defense Academy, Yokosuka, Kanagawa 239-8686, Japan. ando@nda.ac.jp
Yamakita
Mitsuya
M
Yamagata
Zentaro
Z
Koyama
Katsuhiro
K
D000818:Animals; D019328:Buthionine Sulfoximine / Q000008:administration & dosage; D004921:Erythropoietin / Q000096:biosynthesis*; D005978:Glutathione / Q000172:deficiency*; D000860:Hypoxia / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D004921:Erythropoietin; D019328:Buthionine Sulfoximine; D005978:Glutathione