Yamashita N, Nishida M, Hoshida S, Igarashi J, Hori M, Kuzuya T, Tada M
First Department of Medicine, Osaka University Medical School, Japan.
Am J Physiol. 1996 Oct;271(4 Pt 2):H1356-62. doi: 10.1152/ajpheart.1996.271.4.H1356.
We examined whether or not alpha 1-adrenergic stimulation increases the tolerance of the heart to ischemia using a hypoxia-reoxygenation model of cardiac myocytes. After exposure to norepinephrine (NE; 0.2 microM) for 24 h, the manganese superoxide dismutase (Mn-SOD) content and activity in the cells were increased from 0.61 +/- 0.03 to 0.87 +/- 0.04 microgram/dish and 22 +/- 1 to 55 +/- 4 U/dish, respectively. The specific activity of Mn-SOD was also increased from 36 to 63 U/microgram Mn-SOD protein after the stimulation with NE. Prazosin (2 microM) abolished the increase in Mn-SOD activity (U/mg total protein). Creatine kinase (CK) release after hypoxia (PO2 7 mmHg; 3 h)-reoxygenation (1 h) from cells pretreated with NE in the presence of propranolol and yohimbine for 24 h was attenuated by 48% compared with that from cells without NE stimulation. When antisense oligodeoxyribonucleotides to Mn-SOD were added to myocyte cultures, the increase in Mn-SOD activity (U/mg total protein) and the attenuation of CK release after the addition of NE in the presence of propranolol and yohimbine were not observed. These results suggest that alpha 1-adrenergic stimulation increases the tolerance of myocytes to hypoxia through induction and activation of Mn-SOD.
我们使用心肌细胞缺氧复氧模型，研究了α1-肾上腺素能刺激是否会增加心脏对缺血的耐受性。在暴露于去甲肾上腺素（NE；0.2微摩尔）24小时后，细胞中的锰超氧化物歧化酶（Mn-SOD）含量和活性分别从0.61±0.03微克/培养皿增加到0.87±0.04微克/培养皿，以及从22±1单位/培养皿增加到55±4单位/培养皿。在用NE刺激后，Mn-SOD的比活性也从36单位/微克Mn-SOD蛋白增加到63单位/微克Mn-SOD蛋白。哌唑嗪（2微摩尔）消除了Mn-SOD活性（单位/毫克总蛋白）的增加。与未受NE刺激的细胞相比，在普萘洛尔和育亨宾存在的情况下，用NE预处理24小时的细胞在缺氧（PO2 7毫米汞柱；3小时）-复氧（1小时）后的肌酸激酶（CK）释放减少了48%。当向心肌细胞培养物中加入针对Mn-SOD的反义寡脱氧核糖核苷酸时，未观察到Mn-SOD活性（单位/毫克总蛋白）的增加以及在普萘洛尔和育亨宾存在下加入NE后CK释放的减少。这些结果表明，α1-肾上腺素能刺激通过诱导和激活Mn-SOD来增加心肌细胞对缺氧的耐受性。
