Mild Acidosis Protects Neurons during Oxygen-Glucose Deprivation by Reducing Loss of Mitochondrial Respiration.,ACS Chemical Neuroscience

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Mild Acidosis Protects Neurons during Oxygen-Glucose Deprivation by Reducing Loss of Mitochondrial Respiration.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2019-03-13 , DOI: 10.1021/acschemneuro.8b00737
Ming-Yue Zhu ₁ , Dong-Liang Zhang ₁ , Chen Zhou ₁ , Zhen Chai ₁

Affiliation

Brain ischemia is often accompanied by brain acidosis and this acidosis can affect ischemic neuronal injury. Ischemic neuronal injury is initiated by a decrease in ATP production which mainly relies on mitochondrial oxidative phosphorylation. Ischemia often causes mitochondrial dysfunction, and acidosis has been found to affect mitochondrial function, suggesting that acidosis accompanying ischemia may influence neurons by targeting mitochondrial metabolism. However, the effects of acidosis on mitochondrial energy metabolism during ischemia lacks thorough investigation. Here, we found that mild acidosis significantly reduced neuronal death possibly by slowing the process of ATP deprivation during oxygen-glucose deprivation (OGD), an in vitro ischemic model. The maintaining of neuronal ATP depended on protecting mitochondrial ATP production. Further investigation of mitochondrial function revealed that mild acidosis alleviated OGD-induced collapse of mitochondrial membrane potentials as well as damage to respiratory function, at least in part by reducing impacts on complex I and II activities. Inhibition of complex I activity aggravated neuronal death, which suggests that the contribution of mild acidosis to maintaining complex I activity promoted neuronal survival during OGD. Our findings reveal maintaining mitochondrial respiration as a new possible protective mechanism of mild acidosis during ischemia, on neurons.

中文翻译：

轻度酸中毒可通过减少线粒体呼吸损失来保护氧糖剥夺过程中的神经元。

脑缺血常伴有脑酸中毒，这种酸中毒可影响缺血性神经元损伤。缺血性神经元损伤是由ATP产生的减少引起的，ATP的产生主要依赖于线粒体的氧化磷酸化。缺血常引起线粒体功能障碍，发现酸中毒会影响线粒体功能，提示伴随缺血的酸中毒可能通过靶向线粒体代谢来影响神经元。然而，酸中毒对缺血过程中线粒体能量代谢的影响尚缺乏详尽的研究。在这里，我们发现轻度酸中毒可通过减慢体外缺血模型氧葡萄糖剥夺（OGD）期间ATP剥夺的过程来显着减少神经元死亡。维持神经元ATP取决于保护线粒体ATP的产生。线粒体功能的进一步研究表明，轻度酸中毒至少部分通过减少对复杂的I和II活性的影响来缓解OGD诱导的线粒体膜电位的崩溃以及对呼吸功能的损害。抑制复杂I活动加剧了神经元死亡，这表明轻度酸中毒对维持复杂I活动的贡献促进了OGD期间的神经元存活。我们的发现表明，线粒体呼吸的维持是缺血期间神经元轻度酸中毒的一种新的可能的保护机制。抑制复杂I活动加剧了神经元死亡，这表明轻度酸中毒对维持复杂I活动的贡献促进了OGD期间的神经元存活。我们的发现表明，线粒体呼吸的维持是缺血期间神经元轻度酸中毒的一种新的可能的保护机制。抑制复杂I活动加剧了神经元死亡，这表明轻度酸中毒对维持复杂I活动的贡献促进了OGD期间的神经元存活。我们的发现表明，线粒体呼吸的维持是缺血期间神经元轻度酸中毒的一种新的可能的保护机制。

更新日期：2019-03-05

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