Extracellular inosine participates in tumor necrosis factor-alpha induced nitric oxide production in cultured Sertoli cells

Abstract

Recent reports have described purinergic modulation of tumor necrosis factor-alpha (TNF-alpha) signaling in neutrophils and astrocytes. In Sertoli cells, both TNF-R1 and TNF-R2 TNF-alpha receptors are present and this cytokine modulates many functions of these cells related to the maintenance of spermatogenesis. Sertoli cells express distinct purinoreceptors and previous work has shown that these cells secrete extracellular nucleotides and their metabolites. In this work, we studied the possible role of extracellular purines in TNF-alpha signaling in cultured Sertoli cells. This cytokine increased inosine concentration from 30 min to 6 h, with no effect at 24 h. Both TNF-alpha and inosine increased nitrite accumulation and nitric oxide synthase activity. Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, abolished the TNF-alpha induced inosine increase, nitrite accumulation and nitric oxide synthase activity. These results suggest that extracellular inosine acts as intermediary in TNF-alpha stimulated nitric oxide production in cultured Sertoli cells.

Expression of galectin‐3 and its regulation in the testes

“…CAMP responsive element (CRE) and activator protein complex (AP1) have been identified in gal‐3 promoter, an observation which is compatible with the potential direct stimulatory actions of FSH and EGF, respectively, as reported here. Nuclear factor κ B (NF‐ κ B) binding site has been reported in gal‐1 but not in gal‐3 promoter meaning that TNF‐ α effect reported here on Gal‐3 expression is probably exerted in an indirect manner and/or is exerted via another signalling pathway such as, for example, the ERK1/2 and p38 MAPK pathway (de Souza et al. , 2006).…”

Regulation of LPS stimulated ROS production in peritoneal macrophages from alloxan-induced diabetic rats: Involvement of high glucose and PPARγ

“…Nitric oxide production was assayed by quantification of the stable end product of nitric oxide oxidation -nitrite (NO 2 − ) -as previously described (Souza et al, 2006). Briefly, the incubation medium of peritoneal or RAW 264.7 macrophages were collected after the treatments and centrifuged at 12,000 ×g for 10 min.…”

Metabolomic Detection Between Pancreatic Cancer and Liver Metastasis Nude Mouse Models Constructed by Using the PANC1-KAI1/CD82 Cell Line

“…[88][89][90] Extracellular inosine acts as intermediary in tumor necrosis factor-α stimulated nitric oxide production in cultured Sertoli cells. 91 Inosine can suppress the activity of intracellular lactate dehydrogenase (LDH), thus blocking the major source of energy supply of cancer cells. 92 Some studies have reported its inhibitory effect on breast cancer, 93 liver cancer, 94 prostate cancer, 83 and colon cancer.…”