Mitochondrial MPTP: A Novel Target of Ethnomedicine for Stroke Treatment by Apoptosis Inhibition

Abstract

Mammalian mitochondrial permeability transition pore (MPTP), across the inner and outer membranes of mitochondria, is a nonspecific channel for signal transduction or material transfer between mitochondrial matrix and cytoplasm such as maintenance of Ca 2+ homeostasis, regulation of oxidative stress signals, and protein translocation evoked by some of stimuli. Continuous MPTP opening has been proved to stimulate neuronal apoptosis in ischemic stroke. Meanwhile, inhibition of MPTP overopening-induced apoptosis has shown excellent efficacy in the treatment of ischemic stroke. Among of which, the potential molecular mechanisms of drug therapy for stroke has also been gradually revealed by researchers. The characteristics of multi-components or multitargets for ethnic drugs also provide the possibility to treat stroke from the perspective of mitochondrial MPTP. The advantages mentioned above make it necessary for us to explore and clarify the new perspective of ethnic medicine in treating stroke and to determine the specific molecular mechanisms through advanced technologies as much as possible. In this review, we attempt to uncover the relationship between abnormal MPTP opening and neuronal apoptosis in ischemic stroke. We further summarized currently authorized drugs, ethnic medicine prescriptions, herbs, and identified monomer compounds for inhibition of MPTP overopening-induced ischemic neuron apoptosis. Finally, we strive to provide a new perspective and enlightenment for ethnic medicine in the prevention and treatment of stroke by inhibition of MPTP overopeninginduced neuronal apoptosis.

Benzoinum exerts NVU protective effect by inhibiting cell apoptosis in cerebral ischemia rats

“…Apoptosis is an important mechanism of NVU homeostasis regulation [37][38][39]. Bax is a pro-apoptotic signal molecule, while Bcl-2 is an anti-apoptotic signal molecule.…”

Regulation of Cell Death by Mitochondrial Transport Systems of Calcium and Bcl-2 Proteins

“…mPTP/mPTPC (mitochondrial permeability transition pore or mPTP complex): mPTP or mPTPC is considered as the main transport system for Ca 2+ efflux from mitochondria under pathophysiological conditions [ 2 , 3 , 12 , 31 , 32 , 128 , 129 , 130 , 131 , 132 , 133 , 134 ]. Although the mPTPC was initially described in swelling experiments using the fraction of isolated mitochondria and characterized as a non-selective channel that transports ionic and nonionic molecules as early as 1979 [ 110 ], the transport mechanism of this channel actually remains poorly understood.…”

“…The efflux of Ca 2+ occurs through a transient or low conductance opening of mPTP, most likely by lower oligomeric states of mPTP [ 13 , 131 , 162 , 163 , 164 , 165 , 166 , 167 , 168 ]. The evidence for transient opening of mPTP for Ca 2+ was demonstrated by the early studies on the inhibition of Ca 2+ release by Cyclosporin A in isolated adult rat ventricular cardiomyocytes [ 133 ].…”

“…The evidence for transient opening of mPTP for Ca 2+ was demonstrated by the early studies on the inhibition of Ca 2+ release by Cyclosporin A in isolated adult rat ventricular cardiomyocytes [ 133 ]. Transient opening or low conductance opening of the mPTP represent a Ca 2+ efflux mechanism, and various studies have confirmed the essential role of mPTP in the release of Ca 2+ [ 13 , 131 , 164 , 165 , 166 , 167 , 168 ]. mPTP is a nonspecific channel, used by cells in signal transduction and the transfer of molecules between the mitochondrial matrix and cytoplasm.…”

“…mPTP is a nonspecific channel, used by cells in signal transduction and the transfer of molecules between the mitochondrial matrix and cytoplasm. In particular it maintains Ca 2+ homeostasis, regulates oxidative stress signals, and mediates cell death [ 128 , 131 , 169 , 170 ]. Regarding the multi-conductance function of mPTPC, it likely can be assumed that mPTPC is partially oligomerized into a complex with multiple subunits [ 132 , 170 , 171 ].…”