ArticleCell death & disease2016
Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 85 citations in OpenAlex.
- Homocysteine and mitophagy in diabetic retinopathy: unraveling the underlying molecular crosstalk.Endocrine · 2026Review
- From lipid overload to autophagy collapse: how lipid dysregulation drives chronic inflammation and metabolic disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- High-intensity interval training improves cognitive dysfunction in chronically stressed mice through alleviating homocysteine-induced transcriptional repression ofNeurobiology of stress · 2025Article
- ESRRA (estrogen related receptor, alpha) induces ribosomal protein RPLP1-mediated adaptive hepatic translation during prolonged starvation.Autophagy · 2025Article
- Lysosomal acidification impairment in astrocyte-mediated neuroinflammation.Journal of neuroinflammation · 2025Review
- The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood-brain barrier protection.Molecular medicine (Cambridge, Mass.) · 2024Review
- Integrated Multi-Omics Analysis of Cerebrospinal Fluid in Postoperative Delirium.Biomolecules · 2024Article
- Disturbed intracellular folate homeostasis impairs autophagic flux and increases hepatocytic lipid accumulation.BMC biology · 2024Article
- Dietary vitamin B6 intake and stroke are negatively associated in adults: A cross-sectional study from the NHANES.Heliyon · 2024Article
- Cisplatin Nephrotoxicity Is Critically Mediated by the Availability of BECLIN1.International journal of molecular sciences · 2024Article
- Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms.International journal of molecular sciences · 2024Review
- Diet-induced hyperhomocysteinemia causes sex-dependent deficiencies in offspring musculature and brain function.Frontiers in cell and developmental biology · 2024Article
- Defective quality control autophagy in Hyperhomocysteinemia promotes ER stress and consequent neuronal apoptosis through proteotoxicity.Cell communication and signaling : CCS · 2023Article
- Folic acid depletion along with inhibition of the PERK arm of endoplasmic reticulum stress pathway promotes a less aggressive phenotype of hepatocellular carcinoma cells.Molecular and cellular biochemistry · 2023Article
- Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways.Pharmaceutics · 2023Article
- The critical role of the endolysosomal system in cerebral ischemia.Neural regeneration research · 2023Review
- Cerebral Glucose Metabolism and Potential Effects on Endoplasmic Reticulum Stress in Stroke.Aging and disease · 2023Review
- Vitamin D, Folic Acid and Vitamin BNutrients · 2022Article
- A Review on Peripheral Tinnitus, Causes, and Treatments from the Perspective of Autophagy.Experimental neurobiology · 2022Review
- Effect of hyperhomocysteinemia on a murine model of smoke-induced pulmonary emphysema.Scientific reports · 2022Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect. Moreover, HHcy increased unfolded protein response. Interestingly, Vitamin B supplementation restored autophagic flux, alleviated ER stress, and reversed lysosomal dysfunction due to HHCy. Furthermore, the autophagy inducer, rapamycin was able to relieve ER stress and reverse lysosomal dysfunction caused by HHcy in vitro. Inhibition of autophagy by HHcy exacerbated cellular injury during oxygen and glucose deprivation and reperfusion (OGD/R), and oxidative stress. These effects were prevented by Vitamin B co-treatment, suggesting that it may be helpful in relieving detrimental effects of HHcy in ischemia/reperfusion or oxidative stress. Collectively, these findings show that Vitamin B therapy can reverse defects in cellular autophagy and ER stress due to HHcy; and thus may be a potential treatment to reduce ischemic damage caused by stroke in patients with HHcy.
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