ArticleThe Journal of biological chemistry2012
Mesencephalic astrocyte-derived neurotrophic factor protects the heart from ischemic damage and is selectively secreted upon sarco/endoplasmic reticulum calcium depletion.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 1 of them a synthesis that pooled it.
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Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- Neuroprotective and reparative effects of endoplasmic reticulum luminal proteins - mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor.Croatian medical journal · 2019Pooled it
- Sulf1 regulates inflammation via modulation of TGF-β dependent epicardial activation.EMBO reports · 2026Article
- Correlation between serum cerebral dopamine neurotrophic factor levels and severity of coronary artery lesions in acute myocardial infarction.Journal of thoracic disease · 2026Article
- Elevated MANF expression in β cells protects mice from streptozotocin-induced diabetes by attenuating islet stress and immunogenicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Attenuation of epicardial activation and myofibroblast abundance via the Fbln2-Nupr1b axis stimulates cardiac regeneration in zebrafish.Nature cardiovascular research · 2026Article
- Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Neurotrophic Factors: Emerging Biology and Therapeutic Applications for Cardiovascular Diseases.Metabolites · 2026Review
- Advancement in Gene Therapy for the Treatment of Parkinson's Disease: A Comprehensive Review.Mini reviews in medicinal chemistry · 2026Review
- Spatial transcriptomics analysis uncovers ER stress in MANF-deficient Purkinje cells underlying alcohol-induced cerebellar neurodegeneration in mice.Acta neuropathologica communications · 2025Article
- Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.Brain : a journal of neurology · 2025Article
- Paternal Obesity-Induced H3K27me3 Elevation Leads to MANF-Mediated Transgenerational Metabolic Dysfunction in Female Offspring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Investigation of the mesencephalic astrocyte-derived neurotrophic factor-endoplasmic reticulum stress pathway in mood disorders.The international journal of neuropsychopharmacology · 2025Article
- Preclinical models of cardiotoxicity from immune checkpoint inhibitor therapy.Basic research in cardiology · 2025Review
- Article
- Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Mitigates Neuroinflammation and Cognitive Impairment by Modulating Glial Activation in Sepsis-Associated Encephalopathy.Neurochemical research · 2024Article
- Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials.Molecular biology reports · 2024Review
- Utilizing Machine Learning to Identify Biomarkers of Endoplasmic Reticulum Stress and Analyze Immune Cell Infiltration in Parkinson's Disease.Molecular neurobiology · 2024Article
- The neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- MANF serves as a novel hepatocyte factor to promote liver regeneration after 2/3 partial hepatectomy via doubly targeting Wnt/β-catenin signaling.Cell death & disease · 2024Article
- Dual role of neuroplastin in pancreatic β cells: Regulating insulin secretion and promoting islet inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
72 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The endoplasmic reticulum (ER) stress protein mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to protect cells from stress-induced cell death before and after its secretion; however, the conditions under which it is secreted are not known. Accordingly, we examined the mechanism of MANF release from cultured ventricular myocytes and HeLa cells, both of which secrete proteins via the constitutive pathway. Although the secretion of proteins via the constitutive pathway is not known to increase upon changes in intracellular calcium, MANF secretion was increased within 30 min of treating cells with compounds that deplete sarcoplasmic reticulum (SR)/ER calcium. In contrast, secretion of atrial natriuretic factor from ventricular myocytes was not increased by SR/ER calcium depletion, suggesting that not all secreted proteins exhibit the same characteristics as MANF. We postulated that SR/ER calcium depletion triggered MANF secretion by decreasing its retention. Consistent with this were co-immunoprecipitation and live cell, zero distance, photo affinity cross-linking, demonstrating that, in part, MANF was retained in the SR/ER via its calcium-dependent interaction with the SR/ER-resident protein, GRP78 (glucose-regulated protein 78 kDa). This unusual mechanism of regulating secretion from the constitutive secretory pathway provides a potentially missing link in the mechanism by which extracellular MANF protects cells from stresses that deplete SR/ER calcium. Consistent with this was our finding that administration of recombinant MANF to mice decreased tissue damage in an in vivo model of myocardial infarction, a condition during which ER calcium is known to be dysregulated, and MANF expression is induced.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.