谷氨酸诱导的能量代谢调节有助于保护大鼠皮质切片免受缺血性损伤。
Glutamate-induced modulation in energy metabolism contributes to protection of rat cortical slices against ischemia-induced damage.
机构信息
Department of Medical Pharmacology, Faculty of Medicine, Bahcesehir University, Istanbul.
Department of Medical Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey.
出版信息
Neuroreport. 2021 Jan 13;32(2):157-162. doi: 10.1097/WNR.0000000000001572.
OBJECTIVES
Glutamate excitotoxicity contributes to neurodegeneration during cerebral ischemia. Recent studies in the protective effect of glutamate against ischemia and hypoxia have shown the need for questioning the role of glutamate in energy metabolism during ischemia. Current study investigates the effect of glutamate on energy substrate metabolites such as alpha-ketoglutarate, lactate, and pyruvate release during control, oxygen-glucose deprivation (OGD), and reoxygenation (REO) conditions.
METHODS
The effects of 0.5 and 2 mM glutamate on spontaneous alpha-ketoglutarate, lactate, and pyruvate release were tested in vitro, on acute rat cortical slices. Alpha-ketoglutarate, lactate, and pyruvate levels were determined by HPLC with UV detector.
RESULTS
We observed that glutamate added into medium significantly increased alpha-ketogluarate release under control conditions. Although OGD and REO also had a glutamate-like effect, only REO-induced rise further enhanced by glutamate. In contrast to alpha-ketoglutarate, both OGD and REO conditions caused significant declines in pyruvate and lactate outputs. While OGD and REO-induced declines in pyruvate outputs were further potentiated, lactate output was not altered by glutamate added into the medium. Glutamate and alpha-ketoglutarate, moreover, also ameliorated OGD- and REO-induced losses in 2,3,5-triphenyltetrazolium chloride staining with a similar degree.
CONCLUSION
These results indicate that glutamate probably increases alpha-ketoglutarate production as an alternative energy source for use in the TCA cycle under energy-depleted conditions. Thus, increasing the alpha-ketoglutarate production may represent a new therapeutic intervention for neurodegenerative disorders, including cerebral ischemia.
目的
谷氨酸兴奋性毒性导致脑缺血期间的神经退行性变。最近关于谷氨酸对缺血和缺氧的保护作用的研究表明，有必要质疑谷氨酸在缺血期间的能量代谢中的作用。本研究调查了谷氨酸对能量底物代谢物（如α-酮戊二酸、乳酸和丙酮酸）在对照、氧葡萄糖剥夺（OGD）和再氧合（REO）条件下释放的影响。
方法
在体外急性大鼠皮质切片上测试了 0.5 和 2 mM 谷氨酸对自发α-酮戊二酸、乳酸和丙酮酸释放的影响。通过 HPLC 与紫外检测器测定α-酮戊二酸、乳酸和丙酮酸水平。
结果
我们观察到，谷氨酸加入培养基中可显著增加对照条件下的α-酮戊二酸释放。虽然 OGD 和 REO 也具有谷氨酸样作用，但只有 REO 诱导的升高进一步被谷氨酸增强。与α-酮戊二酸相反，OGD 和 REO 条件均导致丙酮酸和乳酸输出显著下降。虽然 OGD 和 REO 诱导的丙酮酸输出下降进一步增强，但谷氨酸加入培养基中并未改变乳酸输出。此外，谷氨酸和α-酮戊二酸还改善了 OGD 和 REO 诱导的 2,3,5-三苯基四唑氯化物染色的损失，其程度相似。
结论
这些结果表明，谷氨酸可能会增加α-酮戊二酸的产生，作为能量耗竭条件下三羧酸循环中替代能量源的使用。因此，增加α-酮戊二酸的产生可能代表治疗神经退行性疾病（包括脑缺血）的新治疗干预措施。
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