S. Zhang and J.-H. Ding contributed equally to this work.
Iptakalim ameliorates MPP+-induced astrocyte mitochondrial dysfunction by increasing mitochondrial complex activity besides opening mitoKATP channels
Article first published online: 11 NOV 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 87, Issue 5, pages 1230–1239, April 2009
How to Cite
Zhang, S., Ding, J.-H., Zhou, F., Wang, Z.-Y., Zhou, X.-Q. and Hu, G. (2009), Iptakalim ameliorates MPP+-induced astrocyte mitochondrial dysfunction by increasing mitochondrial complex activity besides opening mitoKATP channels. J. Neurosci. Res., 87: 1230–1239. doi: 10.1002/jnr.21931
- Issue published online: 23 FEB 2009
- Article first published online: 11 NOV 2008
- Manuscript Accepted: 10 SEP 2008
- Manuscript Revised: 30 JUL 2008
- Manuscript Received: 3 MAY 2008
- National Natural Science Foundation of China. Grant Numbers: 30625038, 30572172
- Key Projects of Natural Science Foundation of Jiangsu Educational Department. Grant Numbers: 05KJA31014, 06KJA31029
- National Key Basic Research Program of China. Grant Number: 2006CB500706
- mitochondrial ATP-sensitive potassium channel opener;
- mitochondrial complex
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 (KATP 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 (mitoKATP) 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 mitoKATP channels. © 2008 Wiley-Liss, Inc.