Iptakalim ameliorates MPP+-induced astrocyte mitochondrial dysfunction by increasing mitochondrial complex activity besides opening mitoKATP channels
✍ Scribed by Shu Zhang; Jian-Hua Ding; Fang Zhou; Zhi-Yuan Wang; Xi-Qiao Zhou; Gang Hu
- Book ID
- 102386030
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 285 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
In addition to the established role of the mitochondrion in energy metabolism, regulation of cell death has been regarded as a major function of this organelle. Our previous studies have demonstrated that iptakalim (IPT), a novel ATP‐sensitive potassium channel (K~ATP~ channel) opener, protects against 1‐methyl‐4‐phenyl‐pyridinium ion (MPP^+^)–induced astrocyte apoptosis via mitochondria and mitogen‐activated protein kinase signal pathways. The present study aimed to investigate whether IPT can protect astrocyte mitochondria against MPP^+^‐induced mitochondrial dysfunction. We showed that treatment with IPT could ameliorate the inhibitory effect of MPP^+^ on mitochondrial respiration and ATP production by using mitochondrial complex I–supported substrates. IPT could also inhibit the increased production of mitochondrial reactive oxygen species (ROS) and the release of cytochrome c from mitochondria induced by MPP^+^. However, mitochondrial ATP‐sensitive potassium (mitoK~ATP~) channel blocker 5‐hydroxydecanoate (5‐HD) could partly abolish all of the above effects of IPT. Because mitochondrial complex dysfunction impairs mitochondrial respiration and ATP production, a further experiment was undertaken to study the effects of IPT on the activity of mitochondrial complex (COX) I and COX IV. It was found that IPT inhibited the decrease in mitochondrial COX I and COX IV activity induced by MPP^+^, but 5‐HD failed to abolish these effects. Taken together, these findings suggest that IPT may protect astrocyte mitochondrial function by regulating complex activity in addition to opening mitoK~ATP~ channels. © 2008 Wiley‐Liss, Inc.