AI Article Synopsis
- The study investigates the role of calpains, specifically m-calpain, in the opening of the mitochondrial permeability transition pore (mPTP) following ischemia-reperfusion injury in rat hearts.
- Researchers found that m-calpain is present in the mitochondrial matrix and is involved in the activation of mPTP, which can lead to cell injury during heart attacks.
- Results showed that calcium (Ca2+) triggers mitochondrial swelling and calpain activation, while the use of a calpain inhibitor significantly reduced these harmful effects, suggesting potential therapeutic approaches for heart damage.
Article Abstract
Background/objectives: Opening of the mitochondrial permeability transition pore (mPTP) is involved in ischemia-reperfusion injury. Isoforms of Ca(2+)-activated cysteine proteases, calpains, are implicated in the development of myocardial infarction in ischemia-reperfusion. Growing evidence has revealed the presence of calpains in the mitochondria. We aimed to characterize mitochondrial calpains in the rat heart and to investigate the roles of calpains in mPTP opening after ischemia-reperfusion.
Methods And Results: Western blotting analysis showed the expression of μ-calpain, m-calpain and calpain 10 in mitochondria isolated from male Sprague-Dawley rats, but casein zymography detected only m-calpain activity. Subcellular fractionation of mitochondria demonstrated the distribution of m-calpain to the matrix fraction. Addition of >500μM of Ca(2+) to isolated mitochondria induced mitochondrial swelling, reflecting mPTP opening, and calpain activation. Ca(2+)-induced mitochondrial swelling was inhibited partially by the calpain inhibitor calpeptin. These results support a partial contribution of calpain in the opening of the mPTP. The addition of Ca(2+) to the mitochondria induced inactivation of complex I of the electron transport chain, and cleavage of the ND6 complex I subunit, which were inhibited by calpeptin. Mitochondria isolated from rat hearts that underwent 30min of coronary occlusion followed by 30min of reperfusion showed activation of mitochondrial calpains, ND6 cleavage, complex I inactivation, and mPTP opening, which were inhibited by pretreatment with calpain inhibitor 1.
Conclusions: We demonstrated for the first time the presence of mitochondrial matrix m-calpain, and its contribution to complex I inactivation and mPTP opening after postischemic reperfusion in the rat heart.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijcard.2015.06.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dynamin-Related Protein 1 Orchestrates Inflammatory Responses in Periodontal Macrophages via Interaction With Hexokinase 1.
J Clin Periodontol
January 2025
Department of Oral Implantology, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.
Aim: To explore the potential roles of mitochondrial dysfunction in the initiation of inflammation in periodontal macrophages and to determine the mechanism underlying the involvement of dynamin-related protein 1 (Drp1) in macrophage inflammatory responses through its interaction with hexokinase 1 (HK1).
Materials And Methods: Gingival tissues were collected from patients diagnosed with periodontitis or from healthy volunteers. Drp1 tetramer formation and phosphorylation were analysed using western blot.
Programmed cell death (apoptosis) is essential part of the process of tissue regeneration that also plays role in the mechanism of pathology. The phenomenon of fast and transient permeability of mitochondrial membranes by various triggers, known as permeability transition pore (mPTP) leads to the release of proapoptotic proteins and acts as an initial step in initiation of apoptosis. However, a role for mPTP was also suggested for physiology and it is unclear if there is a threshold in number of mitochondria with mPTP which induces cell death and how this mechanism is regulated in different tissues.
View Article and Find Full Text PDFPyridoxal-5-phosphate mitigates age-related metabolic imbalances in the rat heart through the HS/AKT/GSK3β signaling axis.
Mitochondrion
January 2025
The Department of Blood Circulation of Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine. Address: 4, Bogomoletz Str., Kyiv 01024, Ukraine.
Pyridoxal-5-phosphate (PLP) enhances the synthesis of endogenous hydrogen sulfide, a potent regulator of cell metabolism. We used 24-month-old rats to investigate the PLP mitoprotective function in the aging heart. We demonstrated improvement of mitochondrial bioenergetic functions, inhibition of mPTP opening after PLP administration.
View Article and Find Full Text PDFReceptor-Interacting Protein Kinase 3-Mediated Modulation of Endothelial Cell Necroptosis and Mitochondrial Dysfunction through AMPK/Drp1 Signaling Pathway: Insights into the Pathophysiological Mechanisms of Lipopolysaccharide-Induced Acute Lung Injury.
Int J Med Sci
January 2025
Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China.
Article Synopsis
- Ripk3 is key in acute lung injury (ALI) by driving endothelial cell damage and inflammation, although the exact mechanisms are not fully understood.
- Studies using Ripk3-deficient mice revealed that removing Ripk3 improved lung tissue health, decreased inflammation, oxidative stress, and endothelial dysfunction after exposure to lipopolysaccharide (LPS).
- Ripk3 was found to inhibit the AMPK pathway and promote necroptosis in endothelial cells by affecting mitochondrial function, suggesting it could be a target for new treatments for ALI.
Influence of the Microbial Metabolite Acetyl Phosphate on Mitochondrial Functions Under Conditions of Exogenous Acetylation and Alkalization.
Metabolites
December 2024
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya St., 3, Pushchino 142290, Russia.
Background: Acetyl phosphate (AcP) is a microbial intermediate involved in the central bacterial metabolism. In bacteria, it also functions as a donor of acetyl and phosphoryl groups in the nonenzymatic protein acetylation and signal transduction. In host, AcP was detected as an intermediate of the pyruvate dehydrogenase complex, and its appearance in the blood was considered as an indication of mitochondrial breakdown.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!