Extracellular inosine is modulated by H2O2 and protects sertoli cells against lipoperoxidation and cellular injury.
Extracellular purines are involved in the regulation of a wide range of physiological processes, including cytoprotection, ischemic preconditioning, and cell death. These actions are usually mediated via triggering of membrane purinergic receptors, which may activate antioxidant enzymes, conferring cytoprotection. Recently, it was demonstrated that the oxidative stress induced by cisplatin up-regulated A1 receptor expression in rat testes, suggesting an involvement of purinergic signaling in the response of testicular cells to oxidant injury. In this article, we report the effect of hydrogen peroxide on purinergic agonist release by cultured Sertoli cells. Extracellular inosine levels are strongly increased in the presence of H2O2, suggesting an involvement of this nucleoside on Sertoli cells response to oxidant treatment. Inosine was observed to decrease H2O2-induced lipoperoxidaton and cellular injury, and it also preserved cellular ATP content during H2O2 exposure. These effects were abolished in the presence of nucleoside uptake inhibitors, indicating that nucleoside internalisation is essential for its action in preventing cell damage.
Gelain
Daniel Pens
DP
Laboratório de Transdução de Sinal em Células Testiculares, Departamento de Bioquímica, Institute de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
De Souza
Luiz Fernando
LF
Ribeiro
Gisele Roncheti
GR
Zim
Marcelo
M
Jardim
Fernanda Rafaela
FR
Moreira
José Cláudio Fonseca
JC
Bernard
Elena Aida
EA
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007288:Inosine / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009536:Niacinamide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D058892:Adenosine Deaminase Inhibitors; D004791:Enzyme Inhibitors; D016877:Oxidants; D009536:Niacinamide; D013868:Thioinosine; C010192:9-(2-hydroxy-3-nonyl)adenine; D007288:Inosine; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; C001789:4-nitrobenzylthioinosine; D000225:Adenine