Mitophagy in Ischaemia/Reperfusion Induced Cerebral Injury

Liu, Kangyong; Sun, Yinyi; Gu, Zhaohua; Shi, Nan; Zhang, Ting; Sun, Xiaojiang

doi:10.1007/s11064-013-1033-0

Cited by 25 publications

(12 citation statements)

References 55 publications

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“…Nonetheless, an increase in LC3B-II on the first day post-ischemia has been reported in neuronal degeneration ( Adhami et al, 2006 ; Li and McCullough, 2010 ), and it has been suggested that the pharmacological inhibition of autophagy reduces cerebral infarct volume ( Kubota et al, 2010 ; Meloni et al, 2011 ; Gao et al, 2012 ). However, autophagic activity may play an important role in neuroprotection after an ischemic event, resulting in a beneficial effect on the cerebral cortex and hippocampus to prevent protein aggregation after stroke ( Rami, 2009 ; Guo et al, 2010 ; Liu et al, 2010 , 2013a , b ; Zhou et al, 2011 ), and autophagic degradation has been proposed as an important regulator of hyperphosphorylated tau levels after an acute injury (e.g., in CI; Liu et al, 2010 ; Marino et al, 2011 ; Schaeffer and Goedert, 2012 ), which is consistent with our findings.…”

Section: Discussionsupporting

confidence: 91%

Comparative analysis of autophagy and tauopathy related markers in cerebral ischemia and Alzheimerâ€™s disease animal models

Villamil-Ortiz

Cardona‐Gómez

2015

Front. Aging Neurosci.

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Alzheimer’s disease (AD) and cerebral ischemia (CI) are neuropathologies that are characterized by aggregates of tau protein, a hallmark of cognitive disorder and dementia. Protein accumulation can be induced by autophagic failure. Autophagy is a metabolic pathway involved in the homeostatic recycling of cellular components. However, the role of autophagy in those tauopathies remains unclear. In this study, we performed a comparative analysis to identify autophagy related markers in tauopathy generated by AD and CI during short-term, intermediate, and long-term progression using the 3xTg-AD mouse model (aged 6,12, and 18 months) and the global CI 2-VO (2-Vessel Occlusion) rat model (1,15, and 30 days post-ischemia). Our findings confirmed neuronal loss and hyperphosphorylated tau aggregation in the somatosensory cortex (SS-Cx) of the 3xTg-AD mice in the late stage (aged 18 months), which was supported by a failure in autophagy. These results were in contrast to those obtained in the SS-Cx of the CI rats, in which we detected neuronal loss and tauopathy at 1 and 15 days post-ischemia, and this phenomenon was reversed at 30 days. We proposed that this phenomenon was associated with autophagy induction in the late stage, since the data showed a decrease in p-mTOR activity, an association of Beclin-1 and Vps34, a progressive reduction in PHF-1, an increase in LC3B puncta and autophago-lysosomes formation were observed. Furthermore, the survival pathways remained unaffected. Together, our comparative study suggest that autophagy could ameliorates tauopathy in CI but not in AD, suggesting a differential temporal approach to the induction of neuroprotection and the prevention of neurodegeneration.

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Section: Discussionsupporting

confidence: 91%

Comparative analysis of autophagy and tauopathy related markers in cerebral ischemia and Alzheimerâ€™s disease animal models

Villamil-Ortiz

Cardona‐Gómez

2015

Front. Aging Neurosci.

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“…Autophagy is the only mechanism by which entire organelles are engulfed and recycled through the lysosomal pathway (Liu et al, 2013). Mitophagy refers to a specific autophagic phenomenon, in which cells are selectively cleared of damaged mitochondria through autophagy (Yang and Klionsky, 2010;Fimia et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells

et al. 2020

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Ferulic acid protects against cardiac injury by scavenging free radicals. However, the role of mitophagy in ferulic acid-induced cardioprotection remains obscure. In the present study, H9c2 cells were exposed to hypoxia/reoxygenation and ferulic acid treatment during hypoxia. We illustrated the impact of ferulic acid on oxidative damage in H9c2 cells. Our results showed that ferulic acid significantly attenuated apoptosis induced by hypoxia/reoxygenation injury and reduced mitochondrial dysfunction, evidenced by a decline in the overproduction of reactive oxygen species and ATP depletion and recovery of the membrane potential. We also found that mitophagy, a selective form of autophagy, was excessively activated in H9c2 cells subjected to hypoxia/reoxygenation. Ferulic acid reduced the binding of mitochondria to lysosomes, down-regulated the PINK1/Parkin pathway, and was accompanied by increased p62 and decreased LC3-II/LC3-I levels. Ferulic acid also antagonistically reduced the activation of mitophagy by rapamycin. These findings suggest that ferulic acid may protect H9c2 cells against ischemia/reperfusion injury by suppressing PINK1/Parkin-dependent mitophagy. Accordingly, our findings may provide a potential target and powerful reference for ferulic acid in clinical prevention and treatment of hypoxia/reoxygenation injury.

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“…Nevertheless, mitochondrial damage was alleviated indicating relative integrity of cristae structure, and a few structures of autophagy and mitophagy appeared in the XXMD- or CsA-treated group. Mitochondria are those essential organelles for generation and action of reactive oxygen species (ROS) in brain cells [ 36 ]. Damaged mitochondria following ischemia and reperfusion could result in the increase in ROS, and meanwhile, mitochondrial ATP levels are considered an indicator of cell death [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury

Lan

Zhang

et al. 2018

Behavioural Neurology

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We investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial function in cerebral ischemia-reperfusion injury. Rats were randomly divided into 5 groups: sham, ischemia and reperfusion (IR), IR plus XXMD (60 g/kg/day) (XXMD60), IR plus cyclosporin A (10 mg/kg/day) (CsA), and IR plus vehicle (Vehicle). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion (MCAO). Cerebral infarct areas were measured by triphenyl tetrazolium chloride staining. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining (HE) and Nissl staining. Ultrastructural features of mitochondria and mitophagy in the penumbra of the ischemic cortex were observed by transmission electron microscopy. Mitophagy was detected by immunofluorescence labeled with LC3B and VDAC1. Autophagy lysosome formation was observed by immunofluorescence labeled with LC3B and Lamp1. The expression of LC3B, Beclin1, and Lamp1 was analyzed by Western blot. The rats subjected to MCAO showed worsened neurological score and cell ischemic damage. These were all significantly reversed by XXMD or CsA. Moreover, XXMD/CsA notably downregulated mitophagy and reduced the increase in LC3, Beclin1, and Lamp1 expression induced by cerebral ischemia and reperfusion. The findings demonstrated that XXMD exerted neuroprotective effect via downregulating LC3, Beclin1, Lamp1, and mitochondrial p62 expression level, thus leading to the inhibition of mitophagy.

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Mitophagy in Ischaemia/Reperfusion Induced Cerebral Injury

Cited by 25 publications

References 55 publications

Comparative analysis of autophagy and tauopathy related markers in cerebral ischemia and Alzheimerâ€™s disease animal models

Comparative analysis of autophagy and tauopathy related markers in cerebral ischemia and Alzheimerâ€™s disease animal models

Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells

Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury

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