Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and modulating JNK and p38 mitogen-activated protein kinase pathways
Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and modulating JNK and p38 mitogen-activated protein kinase pathways
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DOI：
10.1016/j.biocel.2009.01.002
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发表时间：
2009-07-01
影响因子：
4
通讯作者：
Chan, Juliana C. N.
中科院分区：
文献类型：
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作者：
Li, Xiao-Ling;Xu, Gang;Chan, Juliana C. N.
广泛认为人胰岛淀粉样多肽（hIAPP）聚集在产生胰岛素的胰腺β细胞的损失中起重要作用。hIAPP所包含的细胞毒性是由活性氧（ROS）的产生介导的。藻蓝蛋白（PC）是一种来自蓝绿藻的天然化合物，被广泛用作食品补充剂。目前，关于PC对hIAPP存在的β细胞的影响知之甚少。本研究的目的是探讨PC对INS-1 E大鼠胰岛β细胞对hIAPP诱导的细胞死亡的保护作用及其机制。我们的研究结果表明，hIAPP诱导的细胞死亡的凋亡特征，包括生长抑制，染色质凝聚和DNA断裂。然而，通过将细胞与PC共孵育，hIAPP的细胞毒性显著减弱。Western blotting结果显示，PC可阻断hIAPP处理的细胞中caspase-3的激活和聚ADP核糖聚合酶（PARP）的裂解。PC还能显著抑制hIAPP诱导的细胞内ROS和MDA的过度产生，以及超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性的变化。此外，hIAPP触发丝裂原活化蛋白激酶（MAPK）的激活，这些作用被PC有效地抑制。总之，我们的研究结果表明，PC保护INS-1 E胰腺β细胞对hIAPP诱导的细胞凋亡，通过减弱氧化应激和调节c-Jun N-末端激酶（JNK）和p38通路。(c)2009爱思唯尔有限公司保留所有权利。
It is widely accepted that human islet amyloid polypeptide (hIAPP) aggregation plays an important role in the loss of insulin-producing pancreatic beta cells. hIAPP-incluced cytotoxicity is mediated by generation of reactive oxygen species (ROS). Phycocyanin (PC) is a natural compound from blue-green algae that is widely used as food supplement. Currently, little is known about the effects of PC on beta cells with the presence of hIAPP. The aim of this study was to investigate the in vitro protective effects of PC on INS-1E rat insulinoma beta cells against hIAPP-induced cell death, as well as the underlying mechanisms. Our results showed that hIAPP-induced cell death with apoptotic characteristics including growth inhibition, chromatin condensation and DNA fragmentation. However, cytotoxicity of hIAPP was significantly attenuated by co-incubation of the cells with PC. The results of Western blotting showed that activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) in hIAPP-treated cells was blocked by PC. Moreover, PC significantly prevented the hIAPP-incluced overproduction of intracellular ROS and malondialdehyde (MDA), as well as changes in activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Furthermore, hIAPP triggered the activation of mitogen-activated protein kinases (MAPKs), and these effects were effectively suppressed by PC. Taken together, our results suggest that PC protects INS-1E pancreatic beta cells against hIAPP-induced apoptotic cell death through attenuating oxidative stress and modulating c-Jun N-terminal kinase (JNK) and p38 pathways. (c) 2009 Elsevier Ltd. All rights reserved.