ArticleCell death & disease2017
Inhibition of autophagy blocks cathepsins-tBid-mitochondrial apoptotic signaling pathway via stabilization of lysosomal membrane in ischemic astrocytes.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- Dilating the aging clock with light.Innovation (Cambridge (Mass.)) · 2026Review
- PIP4K2A Attenuates Cerebral Ischemia/Reperfusion Injury by Reducing the TRIB3-p62 Complex Burden and Modulating AKT/mTOR Signaling.Translational stroke research · 2026Article
- The effect of astrocyte depletion and repopulation approaches in pathological condition of CNS.Acta neurologica Belgica · 2026Review
- Astrocytic SIRT1 ameliorates cognitive deficits after traumatic brain injury via autophagy-mediated MEGF10 phagocytosis.Journal of neuroinflammation · 2025Article
- Protective effect and molecular mechanisms of magnolol in ischemic stroke.Pharmacological reports : PR · 2025Review
- Inhibition of Cathepsin B Ameliorates Murine Cognitive Dysfunction and Neuronal Damage in Ischemic Stroke by Inhibiting Mitochondrial Apoptosis and Drp1-Mediated Mitochondrial Fission.Molecular neurobiology · 2025Article
- Exploring the role of Cathepsin S in mitochondrial energy metabolism: implications for cancer progression and therapeutic targeting.Medical oncology (Northwood, London, England) · 2025Review
- Role of Atg3, Atg5 and Atg12 in the crosstalk between apoptosis and autophagy in the posterior silk gland of Bombyx mori.Insect molecular biology · 2025Article
- Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells.European journal of medical research · 2025Article
- TSG-6 Protects Against Cerebral Ischemia-Reperfusion Injury via Upregulating Hsp70-1B in Astrocytes.CNS neuroscience & therapeutics · 2025Article
- Exosomes: an innovative therapeutic target for cerebral ischemia-reperfusion injury.Frontiers in pharmacology · 2025Review
- MIF Inhibition by ISO-1 Decreased Autophagic Activity in Primary Astrocytes During Cobalt Chloride-Induced Hypoxia.Current issues in molecular biology · 2024Article
- Ischemic Stroke and the Biological Hallmarks of Aging.Aging and disease · 2024Review
- The underlying mechanism of calcium toxicity-induced autophagic cell death and lysosomal degradation in early stage of cerebral ischemia.Anatomy & cell biology · 2024Review
- The Dual Role of Autophagy in Postischemic Brain Neurodegeneration of Alzheimer's Disease Proteinopathy.International journal of molecular sciences · 2023Review
- RIPK1 inhibition contributes to lysosomal membrane stabilization in ischemic astrocytes via a lysosomal Hsp70.1B-dependent mechanism.Acta pharmacologica Sinica · 2023Article
- Identification of hypoxia-related genes and exploration of their relationship with immune cells in ischemic stroke.Scientific reports · 2023Article
- Phosphorylation of STAT3 at Tyr705 contributes to TFEB-mediated autophagy-lysosomal pathway dysfunction and leads to ischemic injury in rats.Cellular and molecular life sciences : CMLS · 2023Article
- The critical role of the endolysosomal system in cerebral ischemia.Neural regeneration research · 2023Review
- Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways.Cell death & disease · 2023Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous study and others have demonstrated that autophagy is activated in ischemic astrocytes and contributes to astrocytic cell death. However, the mechanisms of ischemia-induced autophagy remain largely unknown. In this study, we established a rat's model of permanent middle cerebral artery occlusion (pMCAO) and an in vitro oxygen and glucose deprivation (OGD) model. Autophagy was inhibited by either pharmacological treatment with 3-methyladenine (3-MA) and wortmannin (Wort) or genetic treatment with knockdown of Atg5 in primary cultured astrocytes and knockout of Atg5 in mouse embryonic fibroblast (MEF) cells, respectively. We found that pharmacological or genetic inhibition of autophagy reversed pMCAO or OGD-induced increase in LC3-II, active cathepsin B and L, tBid, active caspase-3 and cytoplastic cytochrome c (Cyt-c), and suppressed the injury-induced reduction in mitochondrial Cyt-c in ischemic cortex, in injured astrocytes and MEF cells. Immunofluorescence analysis showed that 3-MA or Wort treatment reversed OGD-induced release of cathepsin B and L from the lysosome to the cytoplasm and activation of caspase-3 in the astrocytes. Furthermore, treatment of 3-MA or Wort decreased OGD-induced increase in lysosomal membrane permeability and enhanced OGD-induced upregulation of lysosomal heat shock protein 70.1B (Hsp70.1B) in astrocytes. Inhibition of autophagy by 3-MA or Wort reduced infarction volume in rats and protected OGD-induced astrocytic cell injury. A non-selective caspase inhibitor z-VAD-fmk or a specific caspase-3 inhibitor Q-DEVD-OPh also rescued OGD-induced astrocytic cell injury. In conclusion, our presenting data suggest that inhibition of autophagy blocks cathepsins-tBid-mitochondrial apoptotic signaling pathway via stabilization of lysosomal membranes, possibly due to upregulation of the lysosomal Hsp70.1B in ischemic astrocytes.
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