Simple question. Would this work for stroke reperfusion?
WHOM DO WE CONTACT TO GET THAT RESEARCH DONE?
It most certainly will not be our fucking failures of stroke associations.
Melatonin attenuates myocardial ischemia reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK‐OPA1 signaling pathways
First published: 05 December 2018
This article has been accepted for publication and undergone full peer
review but has not been through the copyediting, typesetting, pagination
and proofreading process, which may lead to differences between this
version and the Version of Record. Please cite this article as doi:
10.1111/jpi.12542
Abstract
Optic atrophy 1 (OPA1)‐related mitochondrial fusion and
mitophagy are vital to sustain mitochondrial homeostasis under stress
conditions. However, no study has confirmed whether OPA1‐related
mitochondrial fusion/mitophagy is activated by melatonin and,
consequently, attenuates cardiomyocyte death and mitochondrial stress in
the setting of cardiac ischemia reperfusion (I/R) injury. Our results
indicated that OPA1, mitochondrial fusion and mitophagy were
significantly repressed by I/R injury, accompanied by infarction area
expansion, heart dysfunction, myocardial inflammation, and cardiomyocyte
oxidative stress. However, melatonin treatment maintained myocardial
function and cardiomyocyte viability, and these effects were highly
dependent on OPA1‐related mitochondrial fusion/mitophagy. At the
molecular level, OPA1‐related mitochondrial fusion/mitophagy, which was
normalized by melatonin, substantially rectified the excessive
mitochondrial fission, promoted mitochondria energy metabolism,
sustained mitochondrial function and blocked cardiomyocyte
caspase‐9‐involved mitochondrial apoptosis. However, genetic approaches
with cardiac‐specific knockout of OPA1 abolished the beneficial effects
of melatonin on cardiomyocyte survival and mitochondrial homeostasis in vivo and in vitro.
Furthermore, we demonstrated that melatonin affected OPA1 stabilization
via the AMPK signaling pathway and that blockade of AMPK repressed OPA1
expression and compromised the cardioprotective action of melatonin.
Overall, our results confirm that OPA1‐related mitochondrial
fusion/mitophagy is actually modulated by melatonin in the setting of
cardiac I/R injury. Moreover, manipulation of the
AMPK‐OPA1‐mitochondrial fusion/mitophagy axis via melatonin may be a
novel therapeutic approach to reduce cardiac I/R injury.
This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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