ArticlePloS one2014
Reversible blockade of complex I or inhibition of PKCβ reduces activation and mitochondria translocation of p66Shc to preserve cardiac function after ischemia.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Mitochondrial remodeling in heart failure with reduced ejection fraction.Frontiers in physiology · 2026Review
- Mitophagy is induced in human engineered heart tissue after simulated ischemia and reperfusion.Journal of cell science · 2025Article
- Distribution of the p66Shc Adaptor Protein Among Mitochondrial and Mitochondria-Associated Membranes Fractions in Normal and Oxidative Stress Conditions.International journal of molecular sciences · 2024Article
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- Hypothermia Prevents Cardiac Dysfunction during Acute Ischemia Reperfusion by Maintaining Mitochondrial Bioenergetics and by Promoting Hexokinase II Binding to Mitochondria.Oxidative medicine and cellular longevity · 2022Article
- p66shc siRNA Nanoparticles Ameliorate Chondrocytic Mitochondrial Dysfunction in Osteoarthritis.International journal of nanomedicine · 2020Article
- Mitochondria-Associated Endoplasmic Reticulum Membranes in the Pathogenesis of Type 2 Diabetes Mellitus.Frontiers in cell and developmental biology · 2020Review
- Cardiac sodium-dependent glucose cotransporter 1 is a novel mediator of ischaemia/reperfusion injury.Cardiovascular research · 2019Article
- Peroxynitrite nitrates adenine nucleotide translocase and voltage-dependent anion channel 1 and alters their interactions and association with hexokinase II in mitochondria.Mitochondrion · 2019Article
- Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression.Scientific reports · 2019Article
- Telomerase Deficiency Predisposes to Heart Failure and Ischemia-Reperfusion Injury.Frontiers in cardiovascular medicine · 2019Article
- Cardiac Specific Knockout of p53 Decreases ER Stress-Induced Mitochondrial Damage.Frontiers in cardiovascular medicine · 2019Article
- Intermediary metabolism and fatty acid oxidation: novel targets of electron transport chain-driven injury during ischemia and reperfusion.American journal of physiology. Heart and circulatory physiology · 2018Article
- Metformin attenuates ER stress-induced mitochondrial dysfunction.Translational research : the journal of laboratory and clinical medicine · 2017Article
- New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases.British journal of pharmacology · 2017Review
- Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies.Annual review of pharmacology and toxicology · 2017Review
- Lack of Contribution of p66shc and Its Mitochondrial Translocation to Ischemia-Reperfusion Injury and Cardioprotection by Ischemic Preconditioning.Frontiers in physiology · 2017Article
- Mitochondrial VDAC1: A Key Gatekeeper as Potential Therapeutic Target.Frontiers in physiology · 2017Review
- Ischemia/Reperfusion.Comprehensive Physiology · 2016Review
- Mitochondrial redox status as a target for cardiovascular disease.Current opinion in pharmacology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aimExcess mitochondrial reactive oxygen species (mROS) play a vital role in cardiac ischemia reperfusion (IR) injury. P66Shc, a splice variant of the ShcA adaptor protein family, enhances mROS production by oxidizing reduced cytochrome c to yield H2O2. Ablation of p66Shc protects against IR injury, but it is unknown if and when p66Shc is activated during cardiac ischemia and/or reperfusion and if attenuating complex I electron transfer or deactivating PKCβ alters p66Shc activation during IR is associated with cardioprotection.
methodsIsolated guinea pig hearts were perfused and subjected to increasing periods of ischemia and reperfusion with or without amobarbital, a complex I blocker, or hispidin, a PKCβ inhibitor. Phosphorylation of p66Shc at serine 36 and levels of p66Shc in mitochondria and cytosol were measured. Cardiac functional variables and redox states were monitored online before, during and after ischemia. Infarct size was assessed in some hearts after 120 min reperfusion.
resultsPhosphorylation of p66Shc and its translocation into mitochondria increased during reperfusion after 20 and 30 min ischemia, but not during ischemia only, or during 5 or 10 min ischemia followed by 20 min reperfusion. Correspondingly, cytosolic p66Shc levels decreased during these ischemia and reperfusion periods. Amobarbital or hispidin reduced phosphorylation of p66Shc and its mitochondrial translocation induced by 30 min ischemia and 20 min reperfusion. Decreased phosphorylation of p66Shc by amobarbital or hispidin led to better functional recovery and less infarction during reperfusion.
conclusionOur results show that IR activates p66Shc and that reversible blockade of electron transfer from complex I, or inhibition of PKCβ activation, decreases p66Shc activation and translocation and reduces IR damage. These observations support a novel potential therapeutic intervention against cardiac IR injury.
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