Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia.
Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia.
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阿格列扎是一种双过氧化物酶体增殖物激活受体α和γ激动剂，可保护心肌细胞免受高血糖的不利影响。
DOI：
10.1177/1479164116679081
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发表时间：
2017-03
影响因子：
2.4
通讯作者：
Qian J
中科院分区：
文献类型：
--
作者：
Chen Y;Chen H;Birnbaum Y;Nanhwan MK;Bajaj M;Ye Y;Qian J
评估阿格列扎对高血糖诱导的细胞凋亡的影响。我们在正常血糖或高血糖条件下（葡萄糖 25 mM）培养人类心肌细胞、心脏特异性过氧化物酶体增殖物激活受体-γ 敲除小鼠或野生型小鼠的心肌细胞。用不同浓度的Aleglitazar处理细胞48小时。我们测量了处理后的心肌细胞的活力、细胞凋亡、caspase-3 活性、细胞色素 C 释放、总抗氧化能力和活性氧形成。用针对过氧化物酶体增殖物激活受体-α或过氧化物酶体增殖物激活受体-γ的短干扰RNA转染人心肌细胞。阿格列扎可减弱高血糖诱导的细胞凋亡、caspase-3 活性和细胞色素 C 释放，并增加人心肌细胞、心脏特异性过氧化物酶体增殖物激活受体-γ 敲除和野生型小鼠心肌细胞的活力。高血糖降低了抗氧化能力，阿格列扎显着削弱了这种作用。阿格列扎可减弱人心肌细胞和野生型小鼠心肌细胞中高血糖诱导的活性氧产生。阿格列扎改善了暴露于高血糖的细胞的细胞活力。单独针对过氧化物酶体增殖物激活受体-α的短干扰RNA和单独针对过氧化物酶体增殖物激活受体-γ的短干扰RNA可部分阻断保护作用，而针对过氧化物酶体增殖物激活受体-α和过氧化物酶体增殖物激活受体-γ的短干扰RNA则完全阻断保护作用。在短期体外模型中，阿格列扎通过联合激活过氧化物酶体增殖物激活受体-α 和过氧化物酶体增殖物激活受体-γ 来保护心肌细胞免受高血糖诱导的细胞凋亡。
To assess the effects of Aleglitazar on hyperglycaemia-induced apoptosis. We incubated human cardiomyocytes, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout or wild-type mice in normoglycaemic or hyperglycaemic conditions (glucose 25 mM). Cells were treated with different concentrations of Aleglitazar for 48 h. We measured viability, apoptosis, caspase-3 activity, cytochrome-C release, total antioxidant capacity and reactive oxygen species formation in the treated cardiomyocytes. Human cardiomyocytes were transfected with short interfering RNA against peroxisome proliferator-activated receptor-α or peroxisome proliferator-activated receptor-γ. Aleglitazar attenuated hyperglycaemia-induced apoptosis, caspase-3 activity and cytochrome-C release and increased viability in human cardiomyocyte, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout and wild-type mice. Hyperglycaemia reduced the antioxidant capacity and Aleglitazar significantly blunted this effect. Hyperglycaemia-induced reactive oxygen species production was attenuated by Aleglitazar in both human cardiomyocyte and wild-type mice cardiomyocytes. Aleglitazar improved cell viability in cells exposed to hyperglycaemia. The protective effect was partially blocked by short interfering RNA against peroxisome proliferator-activated receptor-α alone and short interfering RNA against peroxisome proliferator-activated receptor-γ alone and completely blocked by short interfering RNA to both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ. Aleglitazar protects cardiomyocytes against hyperglycaemia-induced apoptosis by combined activation of both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ in a short-term vitro model.