Hemin induced heme oxygenase-1 over expression involves nuclear factor-E2 related factor-2, nuclear factor-kappaB and extracellular regulated kinase: an experimental study in a testicular torsion-detorsion rodent model.
OBJECTIVE
Nrf2 (nuclear factor-E2 related factor-2), nuclear factor-kappaB and mitogen-activated protein kinase, including extracellular regulated kinase, c-jun N-terminal kinase and p38 mitogen-activated protein kinase, are crucial for signal transduction. We previously reported that heme oxygenase-1 over expression induced by the heme oxygenase-1 inducer hemin protected testes from torsion-detorsion injury. In this study we elucidated which of these enzymes is involved in hemin induced heme oxygenase-1 over expression in testicular tissues after torsion-detorsion injury.


METHODS
Adult male Sprague-Dawley rats (National Science Council, Taipei, Taiwan, Republic of China) were allocated to undergo testicular torsion-detorsion immediately followed by injection of normal saline, hemin or hemin plus tin protoporphyrin, a heme oxygenase-1 inhibitor. Another set of rats that underwent sham operation were used as controls. Testes were harvested 0 and 30 minutes after detorsion and enzyme expression was analyzed.


RESULTS
Hemin alone caused no significant effects on the expression of Nrf2, nuclear factor-kappaB, extracellular regulated kinase and c-jun N-terminal kinase. Similarly testicular torsion-detorsion injury caused no significant effects on Nrf2 expression. In the presence of torsion-detorsion injury hemin significantly up-regulated Nrf2 expression. Moreover, this effect was not affected by tin protoporphyrin. Unlike Nrf2, the expression of nuclear factor-kappaB, extracellular regulated kinase and c-jun N-terminal kinase was significantly up-regulated by testicular torsion-detorsion. Hemin significantly attenuated the testicular torsion-detorsion induced up-regulation of nuclear factor-kappaB and extracellular regulated kinase but not c-jun N-terminal kinase. The effects of hemin on nuclear factor-kappaB and extracellular regulated kinase were significantly reversed by tin protoporphyrin. However, the expression of p38 mitogen-activated protein kinase in rodent testes was not affected by these interventions.


CONCLUSIONS
Hemin induced heme oxygenase-1 over expression in rodent testes after torsion-detorsion injury involves Nrf2, nuclear factor-kappaB and extracellular regulated kinase.
Yang
Stone
S
Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan.
Shih
Hung-Jen
HJ
Chow
Yung-Chiong
YC
Tsai
Pei-Shan
PS
Huang
Chun-Jen
CJ
D000818:Animals; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006427:Hemin / Q000502:physiology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013086:Spermatic Cord Torsion / Q000201:enzymology / Q000378:metabolism*
D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases