Recently, we discovered a novel levodopa-PAK-Tempo conjugate (LPTC) that possess both free radical scavenging properties and mitochondrial-fusion promoting activity. The free radical scavenging activity of LPTC was confirmed in PC12 cell survival assay. In addition, we found that LPTC could restore the mitochondrial tubular network in response to genetically induced fragmentation. The therapeutic potential of LPTC was examined in both in vitro and in vivo experimental ischemia/reperfusion (I/R) models. We demonstrated that LPTC could protect cells from ROS overproduction and inhibit cytochrome c release in a simulated I/R cellular model. Furthermore, we have demonstrated that LPTC could attenuate organ damage induced in a cardiac I/R animal model. Our findings suggest that the protective effect of LPTC reside in maintenance of optimal mitochondrial function by inhibiting mitochondrial oxidative stress and fragmentation.

Novel levodopa-PAK-Tempo conjugate (LPTC) protects the heart against ischemia/reperfusion injury via inhibiting mitochondrial fission and oxidative stress

255th National Meeting (2018)

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