Cellular respiration during hypoxia - Role of cytochrome oxidase as the oxygen sensor in hepatocytes
Cellular respiration during hypoxia - Role of cytochrome oxidase as the oxygen sensor in hepatocytes
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DOI：
10.1074/jbc.272.30.18808
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发表时间：
1997-07-25
影响因子：
4.8
通讯作者：
Schumacker, PT
中科院分区：
文献类型：
--
作者：
Chandel, NS;Budinger, GRS;Schumacker, PT
我们以前报道过肝细胞在长时间缺氧过程中表现出可逆的呼吸抑制（PO 2 = 20 ℃，3-5 h）。此外，当在类似条件下孵育时，分离的牛心细胞色素c氧化酶的表观V-max发生可逆性降低。本研究试图将缺氧诱导的细胞色素氧化酶变化与完整细胞中观察到的呼吸抑制联系起来，在PO 2 = 20 ℃下孵育的肝细胞在2-3小时后表现出呼吸减少和[NAD（P）H]增加，在复氧后逆转N，N，N '，N'-四甲基对苯二胺对缺氧时的呼吸也有抑制作用（0.5 mM）和抗坏血酸（5 mM）用于还原细胞色素c，表明细胞色素氧化酶被部分抑制。同样，缺氧孵育后，肝亚线粒体颗粒显示细胞色素氧化酶的表观Vmax降低44%。在加载四甲基罗丹明乙酯（10 nM）以定量线粒体膜电位的肝细胞中，急性缺氧（
We previously reported that hepatocytes exhibit a reversible suppression of respiration during prolonged hypoxia (PO2 = 20 torr for 3-5 h), Also, isolated bovine heart cytochrome c oxidase undergoes a reversible decrease in apparent V-max when incubated under similar conditions, This study sought to link the hypoxia induced changes in cytochrome oxidase to the inhibition of respiration seen in intact cells, Hepatocytes incubated at PO2 = 20 torr exhibited decreases in respiration and increases in [NAD(P)H] after 2-3 h that were reversed upon reoxygenation (PO2 = 100 torr), Respiration during hypoxia was also inhibited when N,N,N',N'-tetramethyl-p-phenylenediamine (0.5 mM) and ascorbate (5 mM) were used to reduce cytochrome c, suggesting that cytochrome oxidase was partially inhibited. Similarly, liver submitochondrial particles revealed a 44% decrease in the apparent V-max of cytochrome oxidase after hypoxic incubation, In hepatocytes loaded with tetramethylrhodamine ethyl ester (10 nM) to quantify mitochondrial membrane potential, acute hypoxia (