Autophagy in brain ischemia

Kost, Alicja; Kasprowska, Daniela; Łabuzek, Krzysztof; Wiaderkiewicz, Ryszard; Gabryel, Bożena

doi:10.5604/17322693.955650

Cited by 9 publications

(3 citation statements)

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“…Caspase-8-induced pyroptosis occurs simultaneously with NLRP3 activation and IL-1β secretion ( 32 ). Furthermore, as a typical activator, ATP activates the NLRP3 inflammasome in macrophages, leading to caspase-1/GDSDMD-mediated pyroptosis ( 33 ). In addition to caspase-mediated pyroptosis, neutrophil serine endopeptidase activates GSDMD through the cleavage of L-cysteine and activates neutrophils via a mechanism independent of caspase-1/11 ( 34 ).…”

Section: Mechanism Of Pyroptosismentioning

confidence: 99%

Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage

et al. 2022

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Intracerebral hemorrhage (ICH) is a highly harmful neurological disorder with high rates of mortality, disability, and recurrence. However, effective therapies are not currently available. Secondary immune injury and cell death are the leading causes of brain injury and a poor prognosis. Pyroptosis is a recently discovered form of programmed cell death that differs from apoptosis and necrosis and is mediated by gasdermin proteins. Pyroptosis is caused by multiple pathways that eventually form pores in the cell membrane, facilitating the release of inflammatory substances and causing the cell to rupture and die. Pyroptosis occurs in neurons, glial cells, and endothelial cells after ICH. Furthermore, pyroptosis causes cell death and releases inflammatory factors such as interleukin (IL)-1β and IL-18, leading to a secondary immune-inflammatory response and further brain damage. The NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pathway plays the most critical role in pyroptosis after ICH. Pyroptosis can be inhibited by directly targeting NLRP3 or its upstream molecules, or directly interfering with caspase-1 expression and GSDMD formation, thus significantly improving the prognosis of ICH. The present review discusses key pathological pathways and regulatory mechanisms of pyroptosis after ICH and suggests possible intervention strategies to mitigate pyroptosis and brain dysfunction after ICH.

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Section: Mechanism Of Pyroptosismentioning

confidence: 99%

Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage

et al. 2022

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“…When mild ischemia occurs, moderate activation of autophagy, as an important approach of autologous repair, may remove damaged organelles, clean abnormal proteins, prevent aggregation of protein, and inhibit apoptotic cell death. After severe ischemia, continued and excessive autophagy leads to cell death directly and also interacts with the apoptosis signal [10,11]. However, the impact of autophagy induced by cerebral ischemia on NVUs is unknown.…”

Section: Introductionmentioning

confidence: 99%

Autophagy Induced by Oxygen-Glucose Deprivation Mediates the Injury to the Neurovascular Unit

Zhang

Chen

et al. 2019

Med Sci Monit

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Background Autophagy is characterized by the degradation of cellular components in autophagosomes. It plays a significant role in cerebral ischemic injury and has a complex functional connection with apoptosis. The neurovascular unit (NVU) is a structural and functional unit of the nervous system presented as a therapeutic target of stroke. This study aimed to investigate the effect of autophagy induced by ischemic damage on NVUs. Material/Methods SH-SY5Y cells, C6 cells, and rat brain microvascular endothelial cells were cultured with oxygen-glucose deprivation (OGD) exposure for different time durations, and 3-methyladenine (3-MA) was added as an autophagy inhibitor. In all 3 cell lines, lactate dehydrogenase (LDH) release was measured. Furthermore, apoptosis was detected using Annexin V-fluorescein isothiocyanate/propidium iodide labeling and immunofluorescence staining. Autophagosomes were observed through AO/MDC (acridine orange/monodansycadaverine) double staining. LC3-II expression levels were evaluated by western blot analysis. Results In the OGD groups of 3 cell lines, LDH leakage, and apoptotic rates were obviously increased. Remarkable increase in LC3-II expression was found in the OGD groups of SH-SY5Y cells and C6 cells. However, 3-MA decreased the LC3-II expression to varying degrees. Conclusions OGD could induce the over-activation of autophagy and augment the apoptotic activity in neurons and glial cells of NVUs.

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“…Autophagy is an intracellular process involving the degradation of macromolecules and organelles (Kost et al 2011). Autophagy may not only help promote cell survival but also promote cell death through excessive self-digestion and degradation of essential cellular constituents (Reggiori & Klionsky 2002).…”

Section: Introductionmentioning

confidence: 99%

Shengmai injection attenuates the cerebral ischemia/reperfusion induced autophagy via modulation of the AMPK, mTOR and JNK pathways

Yang

Zhou

et al. 2016

Pharmaceutical Biology

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Objective To determine the neuroprotective effect of SMI, we investigated the effect of SMI on cerebral ischemia/reperfusion (I/R) injury in mice as well as the mechanisms underlying this effect. Materials and methods Right middle cerebral artery was occluded by inserting a thread through internal carotid artery for 1 h, and then reperfused for 24 h in mice. The neuroprotective effects were determined using transmission electron microscopic examination, the evaluation of infarct volume, neurological deficits and water brain content. Related mechanisms were evaluated by immunofluorescence staining and western blotting. SMI was injected intraperitoneally after 1 h of ischemia at doses of 1.42, 2.84 and 5.68 g/kg. The control group received saline as the SMI vehicle. Results Results showed that SMI (1.42, 2.84 and 5.68 g/kg) could significantly reduce the infarct volume, SMI (5.68 g/kg) could also significantly improve the neurological deficits, decreased brain water content, as well as the neuronal morphological changes. SMI (5.68g/kg) could significantly inhibit the expression of autophagy-related proteins: Beclin1 and LC3. It also reduced the increase in LC3-positive cells. SMI (5.68 g/ kg) remarkably inhibited the phosphorylation of adenosine monophosphate activated protein kinase (AMPK), and down-regulated the phosphorylation of mammalian target of rapamycin (mTOR) and Jun Nterminal kinase (JNK) after 24 h of reperfusion. Discussion and conclusion The results indicate that SMI provides remarkable protection against cerebral ischemia/reperfusion injury, which may be partly due to the inhibition of autophagy and related signalling pathways. ARTICLE HISTORY

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Autophagy in brain ischemia

Cited by 9 publications

References 0 publications

Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage

Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage

Autophagy Induced by Oxygen-Glucose Deprivation Mediates the Injury to the Neurovascular Unit

Shengmai injection attenuates the cerebral ischemia/reperfusion induced autophagy via modulation of the AMPK, mTOR and JNK pathways

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