Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2020-07-14 , DOI: 10.1016/j.bbagen.2020.129684 Belem Yoval-Sánchez 1 , Luis Francisco Calleja 1 , María de la Luz Hernández-Esquivel 1 , José Salud Rodríguez-Zavala 1
|
Background
Detoxification of aldehydes by aldehyde dehydrogenases (ALDHs) is crucial to maintain cell function. In cardiovascular diseases, reactive oxygen species generated during ischemia/reperfusion events trigger lipoperoxidation, promoting cell accumulation of highly toxic lipid aldehydes compromising cardiac function. In this context, activation of ALDH2, may contribute to preservation of cell integrity by diminishing aldehydes content more efficiently.
Methods
The theoretic interaction of piperlonguminine (PPLG) with ALDH2 was evaluated by docking analysis. Recombinant human ALDH2 was used to evaluate the effects of PPLG on the kinetics of the enzyme. The effects of PPLG were further investigated in a myocardial infarction model in rats, evaluating ALDHs activity, antioxidant enzymes, oxidative stress markers and mitochondrial function.
Results
PPLG increased the activity of recombinant human ALDH2 and protected the enzyme from inactivation by lipid aldehydes. Additionally, administration of this drug prevented the damage induced by ischemia/reperfusion in rats, restoring heart rate and blood pressure, which correlated with protection of ALDHs activity in the tissue, a lower content of lipid aldehydes, and the preservation of mitochondrial function.
Conclusion
Activation of ALDH2 by piperlonguminine ameliorates cell damage generated in heart ischemia/reperfusion events, by decreasing lipid aldehydes concentration promoting cardioprotection.
中文翻译：
Piperlonguminine 是一种新型线粒体醛脱氢酶激活剂，可保护心脏免受缺血/再灌注损伤。
背景
醛脱氢酶 (ALDH) 对醛的解毒对于维持细胞功能至关重要。在心血管疾病中，缺血/再灌注过程中产生的活性氧会引发脂质过氧化，促进细胞内高毒性脂质醛的积累，从而损害心脏功能。在这种情况下，ALDH2 的激活可能通过更有效地减少醛含量来有助于保持细胞完整性。
方法
通过对接分析评估了 Piperlonguminine (PPLG) 与 ALDH2 的理论相互作用。使用重组人 ALDH2 来评估 PPLG 对酶动力学的影响。在大鼠心肌梗死模型中进一步研究了 PPLG 的影响，评估了 ALDH 活性、抗氧化酶、氧化应激标记物和线粒体功能。
结果
PPLG 增加了重组人 ALDH2 的活性，并保护该酶免于被脂醛失活。此外，给予这种药物可以防止大鼠缺血/再灌注引起的损伤，恢复心率和血压，这与保护组织中的 ALDH 活性、降低脂醛含量和保存线粒体功能有关。
结论
Piperlonguminine 激活 ALDH2，通过降低脂醛浓度促进心脏保护，从而改善心脏缺血/再灌注事件中产生的细胞损伤。
京公网安备 11010802027423号