GTP-binding protein-independent potentiation by mastoparan of IL-1β-induced nitric oxide release from insulin-secreting HIT-T15 cells
GTP-binding protein-independent potentiation by mastoparan of IL-1β-induced nitric oxide release from insulin-secreting HIT-T15 cells
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DOI：
10.1023/b:appt.0000018796.52262.b3
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发表时间：
2004-03-01
期刊：
影响因子：
7.2
通讯作者：
Kowluru, A
中科院分区：
文献类型：
--
作者：
Chen, HQ;Veluthakal, R;Kowluru, A
我们最近的数据涉及小分子量G蛋白（例如，H-Ras）在白细胞介素1 β（IL 1 β）诱导的代谢功能障碍和胰岛β细胞凋亡死亡中的作用（Tannous等，Biochem Pharmacol 2001; 62：1459-1468，Kowluru和Morgan，Biochem Pharmacol，2002; 63：1027-1035，Chen等人Biochem Pharmacol，2003; 66：1681-1694）。最近，我们已经证明，来自黄蜂毒液的十四肽mastoparan已经显示直接激活胰岛内源性G蛋白并调节胰岛功能（Amin等人，Endocrinology 2003; 144：4508-4518）。在此，我们调查了潜在的贡献作用，如果有的话，乳甘露聚糖（Mas）敏感的G-蛋白在IL-诱导的一氧化氮（NO）释放胰岛素分泌的HIT-T15细胞。而Mas本身无明显作用，但能显著增强IL诱导的HIT-T15细胞NO释放。有趣的是，Mas-17，一种无活性的Mas类似物，也增强了IL诱导的NO释放，这表明Mas的增强作用可能不涉及特定G蛋白的激活。IL-诱导的NO释放的这种增强作用也证明在另一种聚阳离子化合物，蜂毒肽的存在下。总之，这些发现表明，MAS诱导的增强IL诱导的NO释放可能部分是由于其两亲性和聚阳离子性质。这些数据也保证了在不使用适当的阴性对照（如Mas-17）的情况下，使用Mas研究其对细胞功能的调节时应谨慎。
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.