Paper Caveolin-3 protects diabetic hearts from acute myocardial infarction/reperfusion injury through β2AR, cAMP/PKA, and BDNF/TrkB signaling pathways
Paper Caveolin-3 protects diabetic hearts from acute myocardial infarction/reperfusion injury through β2AR, cAMP/PKA, and BDNF/TrkB signaling pathways
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DOI：
10.18632/aging.103469
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发表时间：
2020-07-31
期刊：
影响因子：
5.2
通讯作者：
Xiao, Feng
中科院分区：
文献类型：
--
作者：
Gong, Jiaji;Zhou, Fan;Xiao, Feng
糖尿病（DM）可增加急性心肌梗死（AMI）后心力衰竭的发生率和病死率。我们试图研究Caveolin-3是否通过cAMP/PKA和BDNF/TrkB信号通路在糖尿病患者MI损伤后显示有益作用。与假手术组和糖尿病组相比，非糖尿病缺血再灌注（I/R）组ADRB 2活性和cAMP/PKA信号通路受损，糖尿病I/R组受损程度更重。在H9 C2细胞中，高糖（HG）刺激通过促进细胞凋亡、抑制细胞活力和抑制TrkB和Akt信号传导进一步增强H/R损伤;相反，ADRB 2激动剂异丙肾上腺素（ISO）显著减弱HG刺激的上述作用。小窝蛋白-3过表达促进ADRB 2在HG刺激的H9 C2细胞膜上的定位，随后抑制凋亡并促进细胞活力。在HG刺激下，Caveolin-3过表达增强cAMP/PKA和BDNF/TrkB信号通路的活性，而ADRB 2沉默逆转Caveolin-3过表达的作用。结论：ADRB 2激动剂可促进H9 C2细胞BDNF/TrkB和cAMP/PKA信号通路的活性，减轻HG加重的H9 C2细胞H/R损伤。Caveolin-3通过β 2AR、cAMP/PKA和BDNF/TrkB信号通路对糖尿病心脏I/R损伤发挥保护作用。
Diabetes mellitus (DM) might increase the incidence and mortality of cardiac failure after acute myocardial infarction (AMI) in patients. We attempted to investigate whether Caveolin-3 showed beneficial effects in DM patient post-MI injury through the cAMP/PKA and BDNF/TrkB signaling pathways. The activity of ADRB2 and cAMP/PKA signaling were impaired in nondiabetic ischemia-reperfusion (I/R) group compared with the sham and DM groups and were more impaired in diabetic I/R group than in the I/R group. In H9C2 cells, high-glucose (HG) stimulation further enhanced H/R injury by promoting cell apoptosis, inhibiting cell viability, and suppressing TrkB and Akt signaling; in contrast, the ADRB2 agonist isoprenaline (ISO) significantly attenuated the above-described effects of HG stimulation. Caveolin-3 overexpression promoted the localization of ADRB2 on the membrane of the HG-stimulated H9C2 cells, subsequently inhibiting apoptosis and promoting cell viability. Under HG stimulation, Caveolin-3 overexpression enhanced the activity of the cAMP/PKA and BDNF/TrkB signaling pathways, whereas ADRB2 silencing reversed the effects of Caveolin-3 overexpression. In conclusion, ADRB2 agonist promoted the activity of the BDNF/TrkB and cAMP/PKA signaling pathways, mitigating the HG-aggravated H/R injuries in H9C2 cells. Caveolin-3 exerts a protective effect on diabetic hearts against I/R damage through the beta 2AR, cAMP/PKA, and BDNF/TrkB signaling pathways.