2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart.
2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart.
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DOI：
10.1038/s41598-022-10168-1
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发表时间：
2022-04-27
影响因子：
4.6
通讯作者：
Holt, Ian J.
中科院分区：
文献类型：
--
作者：
Aiestaran-Zelaia, Irati;Jesus Sanchez-Guisado, Maria;Villar-Fernandez, Marina;Azkargorta, Mikel;Fadon-Padilla, Lucia;Fernandez-Pelayo, Uxoa;Perez-Rodriguez, Diego;Ramos-Cabrer, Pedro;Spinazzola, Antonella;Elortza, Felix;Ruiz-Cabello, Jesus;Holt, Ian J.
2-脱氧-D-葡萄糖（2DG）最近在印度获得紧急批准用于治疗COVID-19，经过成功的临床试验。SARS-CoV-2感染培养细胞伴随糖酵解升高和线粒体功能降低，而2DG抑制糖酵解并刺激呼吸，并限制病毒复制。虽然2DG对培养细胞中的细胞代谢具有多效性作用，但尚不清楚这些作用中的哪一种在体内表现出来。另一方面，已知连续给予2DG可对啮齿动物心脏具有严重的有害影响。在这里，我们表明，延长，间歇性2DG治疗对小鼠的主要影响是增加心脏中的线粒体呼吸链蛋白质组;重要的是，这不会发生空泡化，肥大或纤维化。心脏呼吸链蛋白质组的增加表明线粒体氧化能力的增加，这可以弥补糖酵解抑制引起的能量不足。因此，小鼠心脏中的2DG似乎诱导了一种与SARS-CoV-2感染细胞相反的代谢构型，这可以解释该化合物限制病毒繁殖以使COVID-19患者受益的能力。
2-Deoxy-D-glucose (2DG) has recently received emergency approval for the treatment of COVID-19 in India, after a successful clinical trial. SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. While 2DG has pleiotropic effects on cell metabolism in cultured cells it is not known which of these manifests in vivo. On the other hand, it is known that 2DG given continuously can have severe detrimental effects on the rodent heart. Here, we show that the principal effect of an extended, intermittent 2DG treatment on mice is to augment the mitochondrial respiratory chain proteome in the heart; importantly, this occurs without vacuolization, hypertrophy or fibrosis. The increase in the heart respiratory chain proteome suggests an increase in mitochondrial oxidative capacity, which could compensate for the energy deficit caused by the inhibition of glycolysis. Thus, 2DG in the murine heart appears to induce a metabolic configuration that is the opposite of SARS-CoV-2 infected cells, which could explain the compound’s ability to restrict the propagation of the virus to the benefit of patients with COVID-19 disease.
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影响因子：
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