GLP-1 and Ghrelin Attenuate High Glucose/High Lipid-Induced Apoptosis and Senescence of Human Microvascular Endothelial Cells
GLP-1 and Ghrelin Attenuate High Glucose/High Lipid-Induced Apoptosis and Senescence of Human Microvascular Endothelial Cells
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GLP-1 和 Ghrelin 减弱高糖/高脂诱导的人微血管内皮细胞凋亡和衰老
DOI：
10.1159/000485820
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Zheng, Yuehong
中科院分区：
文献类型：
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作者：
Liao, Pengzhi;Yang, Dan;Zheng, Yuehong
背景/目的：GLP-1和ghrelin是常见的食欲调节激素。两者都具有代谢调节以外的多种功能。然而，GLP-1和ghrelin对内皮生物学的影响尚未完全了解。在这里，我们研究GLP-1和ghrelin在微血管内皮细胞凋亡和衰老中的作用。方法：将人微血管内皮细胞（HMEC）暴露于高糖高脂（HG/HL）环境中，用GLP-1或ghrelin处理。测定细胞凋亡、衰老和线粒体功能。此外，MAPK和Akt信号通路进行了检查。结果如下：GLP-1和ghrelin处理均减少了HG/HL暴露的HMEC中TUNEL阳性细胞的数量，并抑制了caspase-3和PARP裂解以及线粒体功能障碍。GLP-1而非ghrelin减少β-半乳糖苷酶（β-gal）阳性细胞的数量。此外，GLP-1和ghrelin抑制ERK 1/2、JNK 1/2和p38信号传导。GLP-1抑制Akt信号传导，但ghrelin没有影响。此外，JNK 1/2和p38抑制剂，而不是ERK 1/2和Akt抑制剂，减少TUNEL阳性细胞的数量。此外，只有Akt抑制剂减少β-gal阳性细胞的数量。结论：这些结果表明，GLP-1和ghrelin抑制HG/HL条件下的线粒体功能障碍，并通过抑制JNK 1/2和p38信号转导抑制内皮细胞凋亡;此外，GLP-1通过失活Akt信号转导抑制内皮细胞衰老。
Background/Aims: GLP-1 and ghrelin are common appetite-regulating hormones. Both have multiple functions beyond metabolic regulation. However, the effects of GLP-1 and ghrelin on endothelial biology are not fully understood. Here, we investigate the roles of GLP-1 and ghrelin in microvascular endothelial apoptosis and senescence. Methods: Human microvascular endothelial cells (HMECs) were exposed to high glucose/high lipid (HG/HL) conditions and treated with GLP-1 or ghrelin. Cellular apoptosis, senescence, and mitochondrial function were measured. In addition, the MAPK and Akt signaling pathways were examined. Results: Both GLP-1 and ghrelin treatment decreased the number of TUNEL-positive cells and inhibited caspase-3 and PARP cleavage and mitochondrial dysfunction in HG/HL-exposed HMECs. GLP-1, but not ghrelin decreased the number of β-galactosidase (β-gal)-positive cells. Furthermore, GLP-1 and ghrelin inhibited ERK1/2, JNK1/2, and p38 signaling. GLP-1 suppressed Akt signaling, but ghrelin had no effect. Moreover, JNK1/2 and p38 inhibitors, but not ERK1/2 and Akt inhibitors, decreased the number of TUNEL-positive cells. Additionally, only the Akt inhibitor decreased the number of β-gal-positive cells. Conclusion: These results demonstrate that GLP-1 and ghrelin inhibit mitochondrial dysfunction under HG/HL conditions, and suppress endothelial apoptosis via inhibiting JNK1/2 and p38 signaling; moreover, GLP-1 alleviates endothelial senescence via inactivating Akt signaling.