Novel insights into the role of mitochondrial fusion and fission in cardiomyocyte apoptosis induced by ischemia/reperfusion

Li, Yuzhen; Li, Xiuhua

doi:10.1002/jcp.26522

Cited by 46 publications

(37 citation statements)

References 87 publications

(190 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…e previous study of our Journal of Analytical Methods in Chemistry increase the expression of Bcl2 could exhibit neuroprotection against OGD/R injury [26]. Yu also observed this phenomenon in cardiomyocytes [27].…”

Section: Discussionmentioning

confidence: 65%

The Application and Analytical Pathway of Dexmedetomidine in Ischemia/Reperfusion Injury

Tang

Jia

et al. 2019

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

Ischemia/reperfusion cerebral injury can cause serious damage to nerve cells. e injured organelles are cleared by autophagy eventually, which is critical for cell survival. Dexmedetomidine is neuroprotective in various ischemia/reperfusion models. Mitochondrial calcium uniporter (MCU) is the most important channel of mitochondrial Ca 2+ influx into mitochondria, where Ca 2+ has a potential effect on mitochondrial autophagy. However, the role of MCU in the changes of mitophagy and autophagy caused by dexmedetomidine is unknown. In this study, we constructed an in vitro I/R model by subjecting the oxygen and glucose deprivation/reperfusion model to SH-SY5Y cells to mimic the cerebral I/R injury. We found that postconditioning with dexmedetomidine and 3-methyladenine (3MA, an autophagy inhibitor) increased the cell survival meanwhile reduced the production of autophagic vesicles and the expression of LC3 and Beclin 1. is process also increased the expression of BCL-2, P62, and TOM20. After applied with spermine (MCU-specific agonist), the expression of autophagy proteins by dexmedetomidine was reversed, and the same changes were also observed in immunofluorescence. e results of our study suggested that dexmedetomidine can inhibit MCU and reduce excessive mitophagy and autophagy for conferring protection against I/R injury.

show abstract

Section: Discussionmentioning

confidence: 65%

The Application and Analytical Pathway of Dexmedetomidine in Ischemia/Reperfusion Injury

Tang

Jia

et al. 2019

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

show abstract

“…During apoptosis, mitochondria undergo extensive fragmentation, which precedes caspase activation, to release proapoptotic factors [ 36 ]. Excessive fission or decreased fusion contributes to cell apoptosis, while inhibition of mitochondrial fission blocks or delays cell death [ 37 – 40 ]. The GAS-mediated protection of mitochondria from fragmentation might contribute to the decrease in apoptosis in H 2 O 2 -treated H9c2 cells that were pretreated with GAS.…”

Section: Discussionmentioning

confidence: 99%

Gastrodin protects H9c2 cardiomyocytes against oxidative injury by ameliorating imbalanced mitochondrial dynamics and mitochondrial dysfunction

Cheng

Wan

et al. 2020

Acta Pharmacol Sin

View full text Add to dashboard Cite

Gastrodin (GAS) is the main bioactive component of Tianma, a traditional Chinese medicine widely used to treat neurological disorders as well as cardio- and cerebrovascular diseases. In the present study, the protective effects of GAS on H9c2 cells against ischemia–reperfusion (IR)-like injury were found to be related to decreasing of oxidative stress. Furthermore, GAS could protect H9c2 cells against oxidative injury induced by H 2 O 2 . Pretreatment of GAS at 20, 50, and 100 μM for 4 h significantly ameliorated the decrease in cell viability and increase in apoptosis of H9c2 cells treated with 400 μM H 2 O 2 for 3 h. Furthermore, we showed that H 2 O 2 treatment induced fragmentation of mitochondria and significant reduction in networks, footprint, and tubular length of mitochondria; H 2 O 2 treatment strongly inhibited mitochondrial respiration; H 2 O 2 treatment induced a decrease in the expression of mitochondrial fusion factors Mfn2 and Opa1, and increase in the expression of mitochondrial fission factor Fis1. All these alterations in H 2 O 2 -treated H9c2 cells could be ameliorated by GAS pretreatment. Moreover, we revealed that GAS pretreatment enhanced the nuclear translocation of Nrf2 under H 2 O 2 treatment. Knockdown of Nrf2 expression abolished the protective effects of GAS on H 2 O 2 -treated H9c2 cells. Our results suggest that GAS may protect H9c2 cardiomycytes against oxidative injury via increasing the nuclear translocation of Nrf2, regulating mitochondrial dynamics, and maintaining the structure and functions of mitochondria.

show abstract

“…Mitochondria reportedly play an important role in the development of I/R injury, which is involved in calcium homeostasis, oxidative phosphorylation, reactive oxygen species production, and apoptosis [13]. Recent studies have suggested that morphological changes in the mitochondria are relevant to I/R injury [8,22,23]. In stress, the balance of mitochondrial fission and fusion is lost, and fission prevails, which promotes fragmented mitochondria and induces mitochondrial dysfunction [24–26].…”

Section: Discussionmentioning

confidence: 99%

Selective brain hypothermia ameliorates focal cerebral ischemia-reperfusion injury via inhibiting Fis1 in rats

Tang

Chen

Sun

et al. 2019

Preprint

View full text Add to dashboard Cite

13Mitochondrial immoderate fission induces neuronal apoptosis following focal cerebral 14 ischemia-reperfusion (I/R) injury. With fewer complications, selective brain 15 hypothermia (SBH) is considered an effective treatment against neuronal injury after 16 stroke. However, the specific mechanism by which SBH influences mitochondrial 17 fission remains unknown. Mitochondrial fission 1 protein (Fis1), a key factor of the 18 mitochondrial fission system, regulates mitochondrial dynamics. This study aimed to 19 investigate whether SBH regulates Fis1 expression in focal cerebral I/R injury. In this 20 study, rat middle cerebral artery occlusion (MCAO) models were established. After 2 21 h of occlusion, cold saline or normal saline was pumped into rats in different groups 22 through the carotid artery, followed by restoration of blood perfusion. Cortical and 23 rectal temperatures showed that the cold saline treatment achieved SBH. Cerebral I/R 24 injury increased neurological deficit scores(NDS); neuronal apoptosis; Fis1 protein 25 and mRNA expression; cytosolic cytochrome c (cyto-Cyto c) protein expression at 6, 26 24 and 48 h postreperfusion; and cerebral infarct volumes at 24 h postreperfusion. 27 Interestingly, SBH inhibited Fis1 protein and mRNA expression, blocked cyto-Cyto c 28 protein expression, preserved neuronal cell integrity, and reduced neuronal apoptosis. 29 However, normal saline treatment rarely resulted in positive outcomes. Based on 30 these results, SBH inhibited Fis1 expression, thus ameliorating focal cerebral I/R 31 injury in rats.32 3 33 Introduction 34 Stroke is one of the leading causes of death and disability in the world [1-3]. Ischemic 35 stroke caused by cerebral thrombosis or endovascular embolization accounts for a 36 major portion of strokes. Early restoration of blood perfusion is the most effective 37 treatment for stroke; this treatment provides nutrients and oxygen and removes toxic 38 metabolites [4,5]. However, vessel recanalization often exacerbates the existing tissue 39 damage [6,7]; thus, this condition is called cerebral ischemia-reperfusion (I/R) injury. 40 Recent studies have suggested that morphological changes in mitochondria might be 41 relevant to I/R injury [8,9]. Within the cell, mitochondria exist in an ever-changing 42 dynamic state-constant fission and fusion-to form mitochondrial networks and 43 maintain cellular physiological function and survival [10]. Notably, growing evidence 44 has indicated that I/R injury can break this balance to induce neuronal apoptosis 45 [11-13]. Mitochondrial fission protein 1 (Fis1), a 16-kDa protein anchored to the outer 46 membrane of the mitochondria, mediates mitochondrial fission by recruiting 47 cytoplasmic dynamin-related protein1 (Drp1) into the mitochondrial outer membrane 48 [14]. Overexpression of Fis1 increases the frequency of mitochondrial fission, 49 subsequently increasing the release of Cyto c and disrupting mitochondrial membrane 50 potential, thus inducing neuronal apoptosis [15]. In addition, in cells with th...

show abstract

Novel insights into the role of mitochondrial fusion and fission in cardiomyocyte apoptosis induced by ischemia/reperfusion

Cited by 46 publications

References 87 publications

The Application and Analytical Pathway of Dexmedetomidine in Ischemia/Reperfusion Injury

The Application and Analytical Pathway of Dexmedetomidine in Ischemia/Reperfusion Injury

Gastrodin protects H9c2 cardiomyocytes against oxidative injury by ameliorating imbalanced mitochondrial dynamics and mitochondrial dysfunction

Selective brain hypothermia ameliorates focal cerebral ischemia-reperfusion injury via inhibiting Fis1 in rats

Contact Info

Product

Resources

About