Zaidan E, Sims N R
Department of Medical Biochemistry, Flinders University of South Australia, Adelaide.
J Cereb Blood Flow Metab. 1993 Jan;13(1):98-104. doi: 10.1038/jcbfm.1993.12.
Previous studies showed that in rats exposed to 30 min of forebrain ischemia, there were reductions in pyruvate-supported respiration within the first 3 h of recirculation in mitochondria isolated from the dorsolateral striatum (a region in which the majority of neurons are susceptible to ischemia) but not the ischemia-resistant paramedian neocortex. The present study demonstrates that the changes in mitochondrial respiration apparently result from a loss of activity of the pyruvate dehydrogenase complex (PDHC). In mitochondria from the dorsolateral striatum, incubated in the presence of pyruvate and ADP (state 3 conditions) and treated to preserve the phosphorylation state of PDHC, there was no significant change from preischemic activity after 30 min of ischemia or 1 h of recirculation. However, a significant reduction (to 71% of control value) was observed at 3 h of recirculation, and the activity decreased further at 6 and 24 h (to 64 and 43% of control values, respectively). Total PDHC activity in the isolated mitochondria was similarly reduced at 3 h (68% of control values) and 6 h (73% of control values), indicating that the alteration was due to loss or inactivation of the PDHC rather than changes in phosphorylation of the complex. No significant changes were observed in the activity of two other mitochondrial markers, rotenone-sensitive NADH-cytochrome c oxidoreductase and alpha-ketoglutarate dehydrogenase. None of the activities of these three enzymes in mitochondria from the paramedian neocortex was significantly affected by ischemia or recirculation. These results (together with previous observations) indicate an early and specific change affecting the PDHC in cells of the dorsolateral striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明，在经历30分钟前脑缺血的大鼠中，从背外侧纹状体（该区域的大多数神经元易受缺血影响）分离的线粒体在再灌注的最初3小时内，丙酮酸支持的呼吸作用降低，但在抗缺血的正中旁新皮质中则没有。本研究表明，线粒体呼吸的变化显然是由于丙酮酸脱氢酶复合体（PDHC）活性丧失所致。在存在丙酮酸和ADP的情况下（状态3条件）孵育，并经过处理以保持PDHC的磷酸化状态的背外侧纹状体线粒体中，缺血30分钟或再灌注1小时后，与缺血前活性相比没有显著变化。然而，在再灌注3小时时观察到显著降低（降至对照值的71%），并且在6小时和24小时时活性进一步降低（分别降至对照值的64%和43%）。分离的线粒体中的总PDHC活性在3小时（对照值的68%）和6小时（对照值的73%）时同样降低，表明这种改变是由于PDHC的丧失或失活，而不是复合体磷酸化的变化。另外两种线粒体标志物，鱼藤酮敏感的NADH-细胞色素c氧化还原酶和α-酮戊二酸脱氢酶的活性没有观察到显著变化。正中旁新皮质线粒体中这三种酶的活性均未受到缺血或再灌注的显著影响。这些结果（连同先前的观察结果）表明，背外侧纹状体细胞中的PDHC发生了早期特异性变化。（摘要截断于250字）
