ArticleCirculation research2009
Blockade of Hsp20 phosphorylation exacerbates cardiac ischemia/reperfusion injury by suppressed autophagy and increased cell death.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 121 citations in OpenAlex.
- C-terminal extension of HSPB6 in a family with myopathy and cataract.Human molecular genetics · 2026Article
- The Role of Astrocytes in Poststroke Rehabilitation.Brain and behavior · 2025Review
- Review
- HSPA12A maintains aerobic glycolytic homeostasis and Histone3 lactylation in cardiomyocytes to attenuate myocardial ischemia/reperfusion injury.JCI insight · 2024Article
- Circular RNA-circPan3 attenuates cardiac hypertrophy via miR-320-3p/HSP20 axis.Cellular & molecular biology letters · 2024Article
- Autophagy in Heart Failure: Insights into Mechanisms and Therapeutic Implications.Journal of cardiovascular development and disease · 2023Review
- Review
- Unbalanced Redox With Autophagy in Cardiovascular Disease.Journal of lipid and atherosclerosis · 2023Review
- Morroniside inhibits Beclin1-dependent autophagic death and Bax-dependent apoptosis in cardiomyocytes through repressing BCL2 phosphorylation.In vitro cellular & developmental biology. Animal · 2023Article
- Regulation of autophagy of the heart in ischemia and reperfusion.Apoptosis : an international journal on programmed cell death · 2023Review
- Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning.Pharmacological reviews · 2023Review
- Protective and deleterious effects of autophagy in the setting of myocardial ischemia/reperfusion injury: an overview.Molecular biology reports · 2022Review
- Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition, Driving Impaired CaInternational journal of molecular sciences · 2022Article
- Physiological and pathological roles of protein kinase A in the heart.Cardiovascular research · 2022Review
- Protein Quality Control at the Sarcomere: Titin Protection and Turnover and Implications for Disease Development.Frontiers in physiology · 2022Review
- Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases.Frontiers in molecular biosciences · 2022Review
- Role of ATP-Small Heat Shock Protein Interaction in Human Diseases.Frontiers in molecular biosciences · 2022Review
- Review
- The Role of Reactive Oxygen Species, Kinases, Hydrogen Sulfide, and Nitric Oxide in the Regulation of Autophagy and Their Impact on Ischemia and Reperfusion Injury in the Heart.Current cardiology reviews · 2021Review
- The Cardioprotective PKA-Mediated Hsp20 Phosphorylation Modulates Protein Associations Regulating Cytoskeletal Dynamics.International journal of molecular sciences · 2020Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
rationaleThe levels of a small heat shock protein (Hsp)20 and its phosphorylation are increased on ischemic insults, and overexpression of Hsp20 protects the heart against ischemia/reperfusion injury. However, the mechanism underlying cardioprotection of Hsp20 and especially the role of its phosphorylation in regulating ischemia/reperfusion-induced autophagy, apoptosis, and necrosis remain to be clarified.
objectiveHerein, we generated a cardiac-specific overexpression model, carrying nonphosphorylatable Hsp20, where serine 16 was substituted with alanine (Hsp20(S16A)). By subjecting this model to ischemia/reperfusion, we addressed whether: (1) the cardioprotective effects of Hsp20 are associated with serine 16 phosphorylation; (2) blockade of Hsp20 phosphorylation influences the balance between autophagy and cell death; and (3) the aggregation pattern of Hsp20 is altered by its phosphorylation. METHODS AND
resultsOur results demonstrated that Hsp20(S16A) hearts were more sensitive to ischemia/reperfusion injury, evidenced by lower recovery of contractile function and increased necrosis and apoptosis, compared with non-TG hearts. Interestingly, autophagy was activated in non-TG hearts but significantly inhibited in Hsp20(S16A) hearts following ischemia/reperfusion. Accordingly, pretreatment of Hsp20(S16A) hearts with rapamycin, an activator of autophagy, resulted in improvement of functional recovery, compared with saline-treated Hsp20(S16A) hearts. Furthermore, on ischemia/reperfusion, the oligomerization pattern of Hsp20 appeared to shift to higher aggregates in Hsp20(S16A) hearts.
conclusionsCollectively, these data indicate that blockade of Ser16-Hsp20 phosphorylation attenuates the cardioprotective effects of Hsp20 against ischemia/reperfusion injury, which may be attributable to suppressed autophagy and increased cell death. Therefore, phosphorylation of Hsp20 at serine 16 may represent a potential therapeutic target in ischemic heart disease.
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