Protective Effect of Cyclo(His-Pro) on Streptozotocin-Induced Cytotoxicity and Apoptosis In Vitro
Protective Effect of Cyclo(His-Pro) on Streptozotocin-Induced Cytotoxicity and Apoptosis In Vitro
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DOI：
10.4014/jmb.1012.12003
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发表时间：
2011-02-01
影响因子：
2.8
通讯作者：
Choi, Jang Won
中科院分区：
文献类型：
--
作者：
Koo, Kwang Bon;Suh, Hyung Joo;Choi, Jang Won
环（His-Pro）（CHP）是一种天然存在的环状二肽，结构上与促甲状腺激素释放激素（TRH）相关。采用风味蛋白酶和碱性蛋白酶对豆粕进行水解，可有效地制备CHP。在这项研究中，CHP对链脲佐菌素（STZ）诱导的β细胞功能障碍和凋亡的影响进行了研究，在大鼠胰岛素瘤细胞（RINm 5 F）分泌胰岛素。当用2 mM STZ处理RINm 5 F细胞时，胰岛素分泌降低至对照细胞的约54%。然而，CHP处理恢复RINm 5 F细胞的胰岛素分泌活性至未处理的对照细胞的约71%。此外，CHP通过减少STZ诱导的一氧化氮（NO）产生（2.3倍）和脂质过氧化（1.9倍），显着保护细胞免受STZ介导的细胞毒性。此外，CHP处理还减弱了STZ诱导的凋亡事件，如caspase-3的激活，聚（ADP-核糖）聚合酶（PARP）的切割，和DNA片段在RINm 5 F细胞，表明CHP可以保护细胞免于凋亡细胞死亡的STZ氧化应激诱导的抗凋亡蛋白Bcl-2的表达。这些结果表明，CHP可能是一个候选材料的保护和治疗剂对STZ介导的细胞毒性和细胞凋亡。
Cyclo(His-Pro) (CHP) is a naturally occurring, cyclic dipeptide structurally related to thyrotropin-releasing hormone (TRH). CHP was efficiently obtained from soybean meal by hydrolysis with flavourzyme and alcalase. In this study, the effects of CHP on streptozotocin (STZ)-induced beta-cell dysfunction and apoptosis were investigated in rat insulinoma cells (RINm5F) secreting insulin. When the RINm5F cells were treated with 2 mM STZ, insulin secretion decreased to approximately 54% that of control cells. However, CHP treatment restored the insulin-secreting activity of RINm5F cells to approximately 71% that of the untreated control cells. Moreover, CHP significantly protected the cells from STZ-mediated cytotoxicity via reduction of nitric oxide (NO) production (2.3-fold) and lipid peroxidation (1.9-fold), which were induced by STZ. Moreover, CHP treatment also attenuated STZ-induced apoptotic events, such as activation of caspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation in RINm5F cells, indicating that CHP could protect the cells from apoptotic cell death induced by oxidative stress of STZ by increasing the expression of an anti-apoptotic protein, Bcl-2. These results suggest that CHP could be a candidate material for a protective and therapeutic agent against STZ-mediated cytotoxicity and apoptosis.