肺动脉高压中肺动脉平滑肌细胞内缺氧诱导ATP生成从糖酵解向线粒体呼吸转变的证据
Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension.
作者信息
Akagi Satoshi, Nakamura Kazufumi, Kondo Megumi, Hirohata Satoshi, Udono Heiichiro, Nishida Mikako, Saito Yukihiro, Yoshida Masashi, Miyoshi Toru, Ito Hiroshi
机构信息
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
Department of Medical Technology, Graduate School of Health Sciences, Okayama University, Okayama 700-8558, Japan.
出版信息
J Clin Med. 2023 Jul 31;12(15):5028. doi: 10.3390/jcm12155028.
BACKGROUND
The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia.
METHODS
We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology.
RESULTS
Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia.
CONCLUSIONS
There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia.
背景
肺动脉高压（PAH）患者肺动脉平滑肌细胞（PASMCs）的代谢状态尚未完全明确。在本研究中，我们检测了常氧和低氧条件下非PAH-PASMCs和PAH-PASMCs中糖酵解与线粒体呼吸之间的平衡。
方法
我们研究了参与糖酵解和线粒体呼吸的酶，并使用海马细胞外流量技术通过测量细胞外酸化率（ECAR）和细胞耗氧率（OCR）来研究两条主要的能量产生途径（糖酵解和线粒体呼吸）。
结果
与非PAH-PASMCs相比，在常氧和低氧条件下，PAH-PASMCs中丙酮酸脱氢酶激酶1和丙酮酸脱氢酶的mRNA和蛋白水平均升高。与非PAH-PASMCs相比，在常氧条件下PAH-PASMCs中乳酸脱氢酶的mRNA和蛋白水平以及细胞内乳酸浓度也升高。然而，与非PAH-PASMCs相比，在低氧条件下PAH-PASMCs中的这些指标并未显著升高。在常氧条件下，PAH-PASMCs的ATP产生量（59±5 pmol/分钟）显著低于非PAH-PASMCs（70±10 pmol/分钟）。另一方面，在低氧条件下，PAH-PASMCs的ATP产生量（31±5 pmol/分钟）显著高于非PAH-PASMCs（14±3 pmol/分钟）。
结论
在低氧挑战下，产生ATP的代谢策略存在潜在变化。
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