GTP-binding protein-independent potentiation by mastoparan of IL-1beta-induced nitric oxide release from insulin-secreting HIT-T15 cells.
Our recent data implicated small molecular weight G-proteins (e.g., H-Ras) in interleukin 1beta (IL 1beta)-induced metabolic dysfunction and apoptotic demise of the islet beta cell (Tannous et al., Biochem Pharmacol 2001; 62:1459-1468, Kowluru and Morgan, Biochem Pharmacol, 2002; 63:1027-1035, Chen et al. Biochem Pharmacol, 2003; 66:1681-1694). Recently, we have shown that mastoparan, a tetradecapeptide from wasp venom, has been shown to directly activate islet endogenous G-proteins and regulate islet function (Amin et al., Endocrinology 2003; 144: 4508-4518). Herein, we investigated potential contributory roles, if any, of mastoparan (Mas)-sensitive G-proteins in IL-induced nitric oxide (NO) release from insulin-secreting HIT-T15 cells. While, ineffective by itself, Mas significantly potentiated IL-induced NO release from HIT-T15 cells. Interestingly, Mas-17, an inactive analog of Mas, also potentiated IL-induced NO release, suggesting that the potentiating effect of Mas may not involve activation of specific G-proteins. Such potentiating effects on IL-induced NO release were also demonstrable in the presence of another polycationic compound, melittin. Together, these findings suggest that Mas-induced potentiation of IL-induced NO release may in part be due to its amphiphilic and polycationic nature. These data also warrant caution in the use of Mas to study its regulation of cellular function without the use of an appropriate negative control, such as Mas-17.
Department of Pharmaceutical Sciences, Wayne State University, Detroit and beta Cell Biochemistry Laboratory, John D. Dingell VA Medical Center, Detroit, MI 48201, USA.
H-Q
HQ
Chen
R
R
Veluthakal
R
R
Palanivel
A
A
Kowluru
D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008555:Melitten / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010455:Peptides; D014862:Wasp Venoms / Q000494:pharmacology*
D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D009573:Nitrites; D010455:Peptides; D014862:Wasp Venoms; D008555:Melitten; D009569:Nitric Oxide; C037500:mastoparan; D019204:GTP-Binding Proteins