Orchiectomy reduces susceptibility to renal ischemic injury: a role for heat shock proteins.
In previous studies we demonstrated that the presence of testosterone, rather than the absence of estrogen, plays a critical role in gender differences in kidney ischemia/reperfusion (I/R) injury. Although molecular chaperones such as heat shock proteins (HSPs) have been implicated as protective agents in the pathophysiology of I/R injury, their roles in gender differences in susceptibility to renal I/R injury remain to be defined. Here we demonstrate that orchiectomy increases the basal and post-ischemic expression of HSP-27 in kidney tubular epithelial cells, but not HSP-72, glucose-regulated protein (GRP)-78 or GRP-94 expression. Orchiectomy prevents the disruption of the actin cytoskeleton and renal functional disorders induced by I/R, when compared with intact male mice or orchiectomized mice treated with dihydrotestosterone, a non-aromatizable isoform of testosterone. Thus, the protection afforded by orchiectomy is associated with increased expression of HSP-27, a heat shock protein important for maintenance of actin cytoskeletal integrity. These findings indicate that testosterone inhibits the heat shock response and may provide a new paradigm for design of therapies for I/R injury.
Park
Kwon Moo
KM
Department of Anatomy and Pain and Neural Injury Research Center, MRC, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea. kmpark@knu.ac.kr
Cho
Hee Jung
HJ
Bonventre
Joseph V
JV
D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D013196:Dihydrotestosterone / Q000494:pharmacology; D004198:Disease Susceptibility / Q000378:metabolism / Q000601:surgery; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009919:Orchiectomy; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D013739:Testosterone / Q000378:metabolism*
D000199:Actins; D006360:Heat-Shock Proteins; D013196:Dihydrotestosterone; D013739:Testosterone