ArticleCell death & disease2017
Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain.
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 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
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- Assessing the de novo paradigm in sporadic early-onset Alzheimer disease trios.Molecular psychiatry · 2026Article
- DDI-4 induces a temperature-sensitive exocytotic remodeling during C. elegans spermiogenesis via nsun-2-dependent sphingosine signaling.PLoS genetics · 2026Article
- The Role of Sphingosine-1-Phosphate Signaling in Cerebral Ischemia/Reperfusion Injury and Alzheimer's Disease Pathology.International journal of molecular sciences · 2026Review
- TIGAR Suppresses ER Stress-Induced Neuronal Injury through Targeting ATF4 Signaling in Cerebral Ischemia/Reperfusion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- BNIP3-mediated mitophagy attenuates hypoxic-ischemic brain damage in neonatal rats by inhibiting ferroptosis through P62-KEAP1-NRF2 pathway activation to maintain iron and redox homeostasis.Acta pharmacologica Sinica · 2025Article
- Hypomethylated leptin receptor reduces cerebral ischaemia-reperfusion injury by activating the JAK2/STAT3 signalling pathway.The Journal of international medical research · 2024Article
- The Multiple Roles of Autophagy in Neural Function and Diseases.Neuroscience bulletin · 2024Review
- MAM-mediated mitophagy and endoplasmic reticulum stress: the hidden regulators of ischemic stroke.Frontiers in cellular neuroscience · 2024Review
- The Dual Role of Autophagy in Postischemic Brain Neurodegeneration of Alzheimer's Disease Proteinopathy.International journal of molecular sciences · 2023Review
- Astrocyte-derived exosomal nicotinamide phosphoribosyltransferase (Nampt) ameliorates ischemic stroke injury by targeting AMPK/mTOR signaling to induce autophagy.Cell death & disease · 2022Article
- Dapagliflozin as an autophagic enhancer via LKB1/AMPK/SIRT1 pathway in ovariectomized/D-galactose Alzheimer's rat model.Inflammopharmacology · 2022Article
- Injectable cartilage matrix hydrogel loaded with cartilage endplate stem cells engineered to release exosomes for non-invasive treatment of intervertebral disc degeneration.Bioactive materials · 2022Article
- Microglia-induced autophagic death of neurons via IL-6/STAT3/miR-30d signaling following hypoxia/ischemia.Molecular biology reports · 2022Article
- Hemorrhage-Induced Sphingosine Kinase 1 Contributes to Ferroptosis-Mediated Secondary Brain Injury in Intracerebral Hemorrhage.Molecular neurobiology · 2022Article
- Uncovering the 'sphinx' of sphingosine 1-phosphate signalling: from cellular events to organ morphogenesis.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Novel Therapeutic Strategies for Ischemic Stroke: Recent Insights into Autophagy.Oxidative medicine and cellular longevity · 2022Review
- Icariin improves brain function decline in aging rats by enhancing neuronal autophagy through the AMPK/mTOR/ULK1 pathway.Pharmaceutical biology · 2021Article
- Sphingosine 1-Phosphate Receptors in Cerebral Ischemia.Neuromolecular medicine · 2021Review
- Autophagy is Involved in Neuroprotective Effect of Alpha7 Nicotinic Acetylcholine Receptor on Ischemic Stroke.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous findings suggest that sphingosine kinase 2 (SPK2) mediates ischemic tolerance and autophagy in cerebral preconditioning. The aim of this study was to determine by which mechanism SPK2 activates autophagy in neural cells. In both primary murine cortical neurons and HT22 hippocampal neuronal cells, overexpression of SPK2 increased LC3II and enhanced the autophagy flux. SPK2 overexpression protected cortical neurons against oxygen glucose deprivation (OGD) injury, as evidenced by improvement of neuronal morphology, increased cell viability and reduced lactate dehydrogenase release. The inhibition of autophagy effectively suppressed the neuroprotective effect of SPK2. SPK2 overexpression reduced the co-immunoprecipitation of Beclin-1 and Bcl-2, while Beclin-1 knockdown inhibited SPK2-induced autophagy. Both co-immunoprecipitation and GST pull-down analysis suggest that SPK2 directly interacts with Bcl-2. SPK2 might interact to Bcl-2 in the cytoplasm. Notably, an SPK2 mutant with L219A substitution in its putative BH3 domain was not able to activate autophagy. A Tat peptide fused to an 18-amino acid peptide encompassing the native, but not the L219A mutated BH3 domain of SPK2 activated autophagy in neural cells. The Tat-SPK2 peptide also protected neurons against OGD injury through autophagy activation. These results suggest that SPK2 interacts with Bcl-2 via its BH3 domain, thereby dissociating it from Beclin-1 and activating autophagy. The observation that Tat-SPK2 peptide designed from the BH3 domain of SPK2 activates autophagy and protects neural cells against OGD injury suggest that this structure may provide the basis for a novel class of therapeutic agents against ischemic stroke.
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