Welsh N, Sandler S
Department of Medical Cell Biology, Uppsala University, Sweden.
Mol Cell Endocrinol. 1994 Jul;103(1-2):109-14. doi: 10.1016/0303-7207(94)90076-0.
We have presently investigated the putative protective role of hemin against the inhibitory actions of the cytokine interleukin-1 beta (IL-1 beta) on isolated rat pancreatic islets. For this purpose, islets were isolated from adult rats, pre-cultured for 3-7 days in RPMI 1640 medium + 10% fetal calf serum and then exposed to IL-1 beta (5 ng/ml), hemin for 1, 7 or 24 h after which islet nitrite production, aconitase activity, glucose oxidation rates, glucose-stimulated insulin release and medium insulin accumulation were determined. It was found that hemin did not prevent IL-1 beta induced nitrite production. On the other hand, hemin partially counteracted the IL-1 beta induced decrease in aconitase activity, glucose oxidation, insulin release and medium insulin accumulation. This protective effect was present at a hemin concentration of 10 microM and most pronounced at 100 microM. Furthermore, hemin induced the synthesis of a 31 kDa protein, which was shown to be heme oxygenase as demonstrated by Western blot analysis. Finally, the protease inhibitor N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK), which protects against IL-1 beta by decreasing nitric oxide production, was found to act additively in combination with hemin in alleviating the IL-1 beta effects. It is proposed that the beneficial effects of hemin against IL-1 beta could be related to scavenging of nitric oxide and/or an increased resistance to nitric oxide production.
我们目前研究了氯化血红素对细胞因子白细胞介素-1β（IL-1β）对分离的大鼠胰岛抑制作用的假定保护作用。为此，从成年大鼠分离胰岛，在RPMI 1640培养基+10%胎牛血清中预培养3-7天，然后暴露于IL-1β（5 ng/ml）、氯化血红素1、7或24小时，之后测定胰岛亚硝酸盐生成、乌头酸酶活性、葡萄糖氧化率、葡萄糖刺激的胰岛素释放和培养基胰岛素积累。发现氯化血红素不能阻止IL-1β诱导的亚硝酸盐生成。另一方面，氯化血红素部分抵消了IL-1β诱导的乌头酸酶活性、葡萄糖氧化、胰岛素释放和培养基胰岛素积累的降低。这种保护作用在氯化血红素浓度为10μM时出现，在100μM时最为明显。此外，氯化血红素诱导合成一种31 kDa的蛋白质，通过蛋白质印迹分析证明其为血红素加氧酶。最后，发现通过减少一氧化氮生成来保护免受IL-1β影响的蛋白酶抑制剂N-α-甲苯磺酰-L-赖氨酸氯甲基酮（TLCK）与氯化血红素联合使用时在减轻IL-1β作用方面具有相加作用。有人提出，氯化血红素对IL-1β的有益作用可能与一氧化氮的清除和/或对一氧化氮生成的抵抗力增加有关。
