ArticleJournal of molecular and cellular cardiology2018
HAX-1 regulates SERCA2a oxidation and degradation.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- The Landscape of SERCA2 in Cardiovascular Diseases: Expression Regulation, Therapeutic Applications, and Emerging Roles.Biomolecules · 2026Review
- E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
- p22Nature cardiovascular research · 2025Article
- HAX1 inhibits apoptosis and promotes maturation of neutrophils.Cell communication and signaling : CCS · 2025Article
- Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Molecular functions of HAX1 during disease progress.Virus genes · 2024Review
- NADPH Oxidases in Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction.Antioxidants (Basel, Switzerland) · 2022Review
- ER stress and calcium-dependent arrhythmias.Frontiers in physiology · 2022Review
- The thromboxane receptor antagonistFrontiers in cardiovascular medicine · 2022Article
- The Potential of Hsp90 in Targeting Pathological Pathways in Cardiac Diseases.Journal of personalized medicine · 2021Review
- Heat shock protein 47 confers chemoresistance on pancreatic cancer cells by interacting with calreticulin and IRE1α.Cancer science · 2021Article
- Mechanisms underlying pathological CaPflugers Archiv : European journal of physiology · 2021Review
- MicroRNA‑125a‑5p regulates liver cancer cell growth, migration and invasion and EMT by targeting HAX1.International journal of molecular medicine · 2020Article
- The YAP/SERCA2a signaling pathway protects cardiomyocytes against reperfusion-induced apoptosis.Aging · 2020Article
- Hepatic HAX-1 inactivation prevents metabolic diseases by enhancing mitochondrial activity and bile salt export.The Journal of biological chemistry · 2020Article
- Intrinsically disordered HAX-1 regulates CaBiochimica et biophysica acta. Biomembranes · 2020Article
- Increased susceptibility to cardiovascular disease in offspring born from dams of advanced maternal age.The Journal of physiology · 2018Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Ischemia/reperfusion injury is associated with contractile dysfunction and increased cardiomyocyte death. Overexpression of the hematopoietic lineage substrate-1-associated protein X-1 (HAX-1) has been shown to protect from cellular injury but the function of endogenous HAX-1 remains obscure due to early lethality of the knockout mouse. Herein we generated a cardiac-specific and inducible HAX-1 deficient model, which uncovered an unexpected role of HAX-1 in regulation of sarco/endoplasmic reticulum Ca-ATPase (SERCA2a) in ischemia/reperfusion injury. Although ablation of HAX-1 in the adult heart elicited no morphological alterations under non-stress conditions, it diminished contractile recovery and increased infarct size upon ischemia/reperfusion injury. These detrimental effects were associated with increased loss of SERCA2a. Enhanced SERCA2a degradation was not due to alterations in calpain and calpastatin levels or calpain activity. Conversely, HAX-1 overexpression improved contractile recovery and maintained SERCA2a levels. The regulatory effects of HAX-1 on SERCA2a degradation were observed at multiple levels, including intact hearts, isolated cardiomyocytes and sarcoplasmic reticulum microsomes. Mechanistically, HAX-1 ablation elicited increased production of reactive oxygen species at the sarco/endoplasic reticulum compartment, resulting in SERCA2a oxidation and a predisposition to its proteolysis. This effect may be mediated by NAPDH oxidase 4 (NOX4), a novel binding partner of HAX-1. Accordingly, NOX inhibition with apocynin abrogated the effects of HAX-1 ablation in hearts subjected to ischemia/reperfusion injury. Taken together, our findings reveal a role of HAX-1 in the regulation of oxidative stress and SERCA2a degradation, implicating its importance in calcium homeostasis and cell survival pathways.
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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.