Activation of autophagy in rat brain cells following focal cerebral ischemia reperfusion through enhanced expression of Atg1/pULK and LC3

Yu, Jingwei; Cui-fen, Bao; Dong, Yanru; Liu, Xia

doi:10.3892/mmr.2015.3850

Cited by 17 publications

(13 citation statements)

References 24 publications

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“…Our research provided evidence that one of the main pathological changes that occurs following a traumatic brain injury was cerebral edema, which is characterized by an excessive accumulation of water in both the intracellular and extracellular spaces, as a result of which there was a significant increase in brain volume, weight, and intracranial pressure, which could potentially cause brain herniation as well as death [14]. A report also previously showed a significant increase in water content in the ischemic brain tissues [15]. Kappelle et al suggested the notion that there was a high expression in LFA-1 in the hippocampal neurons in rats suffering from acute cerebral ischemia, due to the weakening of the immune, which was consistent with our findings [16].…”

Section: Discussionmentioning

confidence: 87%

Lentivirus-Mediated Gene Silencing of Lymphocyte Function-Associated Antigen 1 Inhibits Apoptosis of Hippocampal Neurons in Rats with Acute Cerebral Ischemia After Cerebral Lymphatic Blockage

Yu¹,

Li²,

Che³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cerebral ischemia is considered to be the most common cause of stroke with high mortality. It occurs as a result of the damage of the hippocampal neurons with lymphocyte function–associated antigen (LFA)-1 being emphasized to play a role in the biological functions of hippocampal neurons. This study was conducted in order to investigate the effects of specific knockdown of LFA-1 expression by lentivirus had on the apoptosis of the hippocampal neurons, simulated by rat models of acute cerebral ischemia after cerebral lymphatic blockage. Methods: A total of 60 Wistar rats were selected as subjects, among which 50 were used to establish models of the acute cerebral ischemia after cerebral lymphatic blockage, while the remaining 10 rats were treated with the sham operation. The underlying regulatory mechanisms regarding LFA-1 were analyzed with the treatment of si-LFA-1 and LFA-1 vector in the hippocampal CA1 area of brain tissues isolated from the rats with acute cerebral ischemia. The brain water content, electrolyte content, and blood-brain barrier permeability located in ischemic area of rats were measured. TUNEL staining and immunochemistry methods were employed in order to determine the apoptosis rate and positive levels of LFA-1, MMP-9, and Caspase-3. The mRNA and protein levels of related genes were also detected by means of RT-qPCR and western blot assay. Results: The brain water content, Na⁺ and Ca⁺ contents, blood-brain barrier permeability, apoptosis rate, positive levels of LFA-1, MMP-9, and Caspase-3 were decreased, and the K⁺ content was increased in ischemic tissues treated with si-LFA-1. The mRNA and protein levels of LFA-1, MMP-9, Caspase-3, and Bax had all decreased, while the mRNA and protein levels of Bcl-2 were elevated in the hippocampal CA1 area of rat brain tissues treated with si-LFA-1. These situations could be reversed through the up-regulation of LFA-1. Conclusion: In conclusion, LFA-1 gene silencing could improve the acute cerebral ischemia after cerebral lymphatic blockage by inhibiting apoptosis of the hippocampal neurons in rats.

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Section: Discussionmentioning

confidence: 87%

Lentivirus-Mediated Gene Silencing of Lymphocyte Function-Associated Antigen 1 Inhibits Apoptosis of Hippocampal Neurons in Rats with Acute Cerebral Ischemia After Cerebral Lymphatic Blockage

Yu¹,

Li²,

Che³

et al. 2018

Cell Physiol Biochem

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“…These findings support the hypothesis that a mitochondrial mechanism may underlie the sex differences in long-term neurobehavioral outcome observed following HI. Mitochondrial fission (or fragmentation) (Pradeep et al, 2014; Zhang et al, 2015; Owens et al, 2015a) and autophagy (Weis et al, 2014; Li et al, 2015; Yu et al, 2015) are known to occur following cerebral ischemia–reperfusion injury. It is hypothesized that mitochondrial fragmentation segregates oxidatively modified mitochondrial proteins for elimination via mitochondrial-specific autophagy (mitophagy) (Twig et al, 2008; Soubannier et al, 2012; Norton et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia–ischemia

et al. 2016

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Males are more susceptible than females to long-term cognitive deficits following neonatal hypoxic-ischemic encephalopathy (HIE). Mitochondrial dysfunction is implicated in the pathophysiology of cerebral hypoxia–ischemia (HI), but the influence of sex on mitochondrial quality control (MQC) after HI is unknown. Therefore, we tested the hypothesis that mitophagy is sexually dimorphic and neuroprotective 20–24 h following the Rice–Vannucci model of rat neonatal HI at postnatal day 7 (PN7). Mitochondrial and lysosomal morphology and degree of co-localization were determined by immunofluorescence in the cerebral cortex. No difference in mitochondrial abundance was detected in the cortex after HI. However, net mitochondrial fission increased in both hemispheres of female brain, but was most extensive in the ipsilateral hemisphere of male brain following HI. Basal autophagy, assessed by immunoblot for the autophagosome marker LC3BI/II, was greater in males suggesting less intrinsic reserve capacity for autophagy following HI. Autophagosome formation, lysosome size, and TOM20/LAMP2 co-localization were increased in the contralateral hemisphere following HI in female, but not male brain. An accumulation of ubiquitinated mitochondrial protein was observed in male, but not female brain following HI. Moreover, neuronal cell death with NeuN/TUNEL co-staining occurred in both hemispheres of male brain, but only in the ipsilateral hemisphere of female brain after HI. In summary, mitophagy induction and neuronal cell death are sex dependent following HI. The deficit in elimination of damaged/dysfunctional mitochondria in the male brain following HI may contribute to male vulnerability to neuronal death and long-term neurobehavioral deficits following HIE.

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“…Autophagy is a way to obtain energy to maintain intracellular energy balance by degrading long-lived proteins and damaged organelles under stress conditions [18]. The occurrence of autophagy is related to autophagy-related gene Open Access Library Journal involved in the induction of autophagy, and its activity was regulated by mTOR [23]. The ULK1 complex includes ULK1, Atg13 and FIP200.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Autophagy Attenuated Cell Damage after OGD/R in SH-SY5Y Cells by Down-Regulating AMPK-Mediated Autophagy Signaling Pathway

Zhang¹,

Liu²

2019

OALib

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Background: Activation of autophagy becomes a new therapeutic target for the treatment of stroke. The aim of this study was to observe the role of autophagy in the model of glucose-oxygen deprivation reoxygenation (OGD/R) in SH-SY5Y cells by interfering with AMPK-mediated autophagy signaling pathway. Methods: The effects of autophagy on OGD/R injury in SH-SY5Y cells were investigated by evaluating cell viability and morphologic change using Cell Counting Kit-8 (CCK-8) and inverted microscop, respectively. To investigate whether autophagy played a role via the AMPK-mTOR signaling pathway, the levels of phospho-AMPK, phospho-mTOR, ULK1, microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 were detected using Western blot. In order to detect changes in autophagic flow after OGD/R, autophagic flux (number of autophagosomes and autophagosomes) was detected by tandem stably expressed a tandem GFP-mRFP-LC3 construct. Results: Autophagy was low in the control group. After OGD/R, the expression of autophagy-related proteins LC3 and Beclin 1 and autophagic flux increased, phospho-AMPK and ULK1 expression increased and phospho-mTOR expression decreased, meanwhile abnormal cell morphological changes increased significantly and cell viability decreased. Inhibition of AMPK activity, the levels of phospho-mTOR, ULK1, LC3, Beclin1 and the expression of autophagic flux were opposite to those of the model group; cell abnormal morphology and structure improved, and cell viability increased. Conclusion: Inhibition of autophagy can attenuate cell damage after OGD/R in SH-SY5Y cells by down-regulating AMPK-mediated autophagy signaling pathway.

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Activation of autophagy in rat brain cells following focal cerebral ischemia reperfusion through enhanced expression of Atg1/pULK and LC3

Cited by 17 publications

References 24 publications

Lentivirus-Mediated Gene Silencing of Lymphocyte Function-Associated Antigen 1 Inhibits Apoptosis of Hippocampal Neurons in Rats with Acute Cerebral Ischemia After Cerebral Lymphatic Blockage

Lentivirus-Mediated Gene Silencing of Lymphocyte Function-Associated Antigen 1 Inhibits Apoptosis of Hippocampal Neurons in Rats with Acute Cerebral Ischemia After Cerebral Lymphatic Blockage

Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia–ischemia

Inhibition of Autophagy Attenuated Cell Damage after OGD/R in SH-SY5Y Cells by Down-Regulating AMPK-Mediated Autophagy Signaling Pathway

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