Exercise and mitochondrial mechanisms in patients with sarcopenia

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 6, 2022

Sarcopenia is a severe loss of muscle mass and functional decline during aging that can lead to reduced quality life, limited patient independence, increased risk falls. The causes sarcopenia include inactivity, oxidant production, reduction antioxidant defense, disruption mitochondrial activity, mitophagy, change in biogenesis. There evidence dysfunction an important cause sarcopenia. Oxidative stress defenses mitochondria form vicious cycle leads the intensification separation, suppression fusion/fission, inhibition electron transport chain, ATP increase DNA damage, biogenesis disorder. On other hand, exercise adds healthy network by increasing markers fusion fission, transforms defective into efficient mitochondria. also decrease dynamics, mitophagy markers, efficiency level ROS apoptosis. In contrast, increases activating genes affected PGC1-ɑ (such as CaMK, AMPK, MAPKs) altering cellular calcium, ATP-AMP ratio, stress. Activation regulates transcription factors TFAM, MEFs, NRFs) formation new networks. Hence, moderate-intensity be used non-invasive treatment for pathways regulate skeletal muscle.

Language: Английский

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Mitochondrial quality control in diabetic cardiomyopathy: from molecular mechanisms to therapeutic strategies

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(14), P. 5276 - 5290

Published: Jan. 1, 2022

In diabetic cardiomyopathy (DCM), a major complication, the myocardium is structurally and functionally altered without evidence of coronary artery disease, hypertension or valvular disease.Although numerous anti-diabetic drugs have been applied clinically, specific medicines to prevent DCM progression are unavailable, so prognosis remains poor.Mitochondrial ATP production maintains energetic requirements cardiomyocytes, whereas mitochondrial dysfunction can induce aggravate by promoting oxidative stress, dysregulated calcium homeostasis, metabolic reprogramming, abnormal intracellular signaling apoptosis in cardiomyocytes.In response dysfunction, quality control (MQC) system (including fission, fusion, mitophagy) activated repair damaged mitochondria.Physiological fission fragments network isolate mitochondria.Mitophagy then allows dysfunctional mitochondria be engulfed autophagosomes degraded lysosomes.However, MQC results excessive impaired fusion delayed mitophagy, causing fragmented accumulate this review, we summarize molecular mechanisms discuss how pathological contributes development.We present promising therapeutic approaches improve progression.

Language: Английский

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IL-6/STAT3 Signaling Promotes Cardiac Dysfunction by Upregulating FUNDC1-Dependent Mitochondria-Associated Endoplasmic Reticulum Membranes Formation in Sepsis Mice

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 8

Published: Jan. 18, 2022

Cytokine storm is closely related to the initiation and progression of sepsis, level IL-6 positively correlated with mortality organ dysfunction. Sepsis-induced myocardial dysfunction (SIMD) one major complications. However, role IL-6/STAT3 signaling in SIMD remains unclear.Septic mice were induced by intraperitoneal injection LPS (10 mg/kg). Echocardiography, cytokines detection, histologic examination showed that sepsis developed cardiac systolic diastolic dysfunction, increase inflammatory serum, activated STAT3 TLR4/NFκB pathway heart, raised apoptosis, which attenuated inhibitor, Bazedoxifene. In vitro, we found decreased cell viability a concentration-dependent manner STAT3. Western blot immunofluorescence results indicated phosphorylation was inhibited Bazedoxifene also suppressed LPS-induced transcription. sIL-6R caused p-STAT3 firstly then significantly increased. More importantly, STAT3-knockdown expression FUNDC1, protein located mitochondria-associated endoplasmic reticulum membranes (MAMs). Overexpression led an FUNDC1 expression. Dual-luciferase reporter assay used confirm potential transcription factor for FUNDC1. Moreover, increased MAMs formation intracellular Ca2+ levels, enhanced Cav1.2 RyR2, mitochondrial membrane ATP promoted fragmentation, mitophagy proteins ROS production H9c2 cells, reversed knockdown inhibitor including Stattic.IL-6/STAT3 plays key through regulating FUNDC1-associated interfering function ER mitochondria. IL-6/STAT3/FUNDC1 could be new therapeutic target SIMD.

Language: Английский

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Dual specificity phosphatase 1 attenuates inflammation-induced cardiomyopathy by improving mitophagy and mitochondrial metabolism

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 64, P. 101567 - 101567

Published: Aug. 6, 2022

Dual specificity phosphatase 1 (DUSP1) is regarded as an anti-inflammatory factor in cardiovascular disorders. Mitophagy removes damaged mitochondria and thus promotes mitochondrial regeneration. We investigated whether DUSP1 could attenuate inflammation-induced cardiomyopathy by improving mitophagy.Lipopolysaccharide was used to induce septic wild-type (WT) transgenic (DUSP1TG) mice.Echocardiography revealed that lipopolysaccharide impaired heart function reducing the cardiac systolic diastolic capacities of WT mice. Freshly isolated single cardiomyocytes from lipopolysaccharide-treated mice also exhibited reduced contractile/relaxation parameters. However, overexpression not only maintained mechanical properties cardiomyocytes, but improved performance. Lipopolysaccharide upregulated myocardial inflammatory gene transcription adhesive expression, which increased neutrophil accumulation cardiomyocyte apoptosis inhibited response therefore promoted survival. disrupted respiration metabolism restored metabolism, membrane potential reactive oxygen species production, possibly increasing FUN14 domain-containing (FUNDC1)-dependent mitophagy. Silencing FUNDC1 abolished protective effects on their following treatment.These results demonstrated a novel protects against FUNDC1-induced

Language: Английский

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DUSP1 interacts with and dephosphorylates VCP to improve mitochondrial quality control against endotoxemia-induced myocardial dysfunction

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(8)

Published: July 18, 2023

Language: Английский

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Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations

Antioxidants, Journal Year: 2022, Volume and Issue: 11(2), P. 231 - 231

Published: Jan. 25, 2022

Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance independent sepsis discriminator mortality predictor intensive care unit (ICU) patients with (n = 145), compared non-infectious critically ill 112) healthy individuals 89). Serum total oxidative status (TOS) antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), selected biomolecules (Ζn, glutathione) correlated apoptotic mediators (caspase-3, capsase-9) central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering TOS, TAC, TOS/TAC all three groups demonstrated. Septic had elevated TOS/TAC, (p 0.001). associated severity scores, procalcitonin, IFN-γ, Hsp72, Hsp90, protein, isoforms -2B, -ΔΕx3, -WT < In a propensity probability (age-sex-adjusted) logistic regression model, only independently (Exp(B) 25.4, p The AUCTOS/TAC (0.96 (95% CI 0.93-0.99)) higher than AUCTAC (z 20, 0.001) or AUCTOS 3.1, 0.002) distinguishing repressed TAC strong predictors 0.01). Oxidant/antioxidant impaired septic trauma surgery related anti-apoptotic, inflammatory, innate immunity alterations. unpredicted might be undefined phenotypes individuals.

Language: Английский

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ALDH2 attenuates myocardial pyroptosis through breaking down Mitochondrion-NLRP3 inflammasome pathway in septic shock

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 13, 2023

Cell survival or death is critical for cardiac function. Myocardial pyroptosis, as a newly recognized programmed cell death, remains poorly understood in sepsis. In this study, we evaluated the effect of aldehyde dehydrogenase (ALDH2) on myocardial pyroptosis and revealed underlying mechanisms We established septic shock mice model by intraperitoneal injection Lipopolysaccharide (LPS, 15 mg/kg) 12 h before sacrifice. It was found that significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation Caspase-1/GSDMD-dependent which remarkably improved rate shock-induced dysfunction, relative to control group. While knockout knockdown aggravated these phenomena. Intriguingly, LPS-induced deacetylation Hydroxyacyl-CoA trifunctional multienzyme complex α subunit (HADHA) suppressing translocation Histone deacetylase (HDAC3) from nuclei mitochondria. Acetylated HADHA essential mitochondrial fatty acid β-oxidation, its interruption can result accumulation toxic lipids, induce mROS cause mtDNA ox-mtDNA release. Our results confirmed role activation. Hdac3 remarkedly suppressed but Hadha eliminated effect. 3, protected ac-HADHA deacetylation, reduced aldehyde, ox-mtDNA, thereby avoided pyroptosis. This study provided novel mechanism through 3/HADHA- pathway demonstrated significant therapeutic target

Language: Английский

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Alterations of the Adipo–Myokine Irisin in Sepsis and Septic Shock: Diagnostic and Prognostic Implications

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 291 - 291

Published: Feb. 29, 2024

Irisin, a novel adipo-myokine with metabolic regulatory functions, exerts anti-inflammatory, antioxidant, and anti-apoptotic actions that may confer protection against sepsis-induced organ injury in experimental studies. Until now, only one human study has explored circulating irisin at sepsis onset. We aimed to examine serum its kinetics critically ill patients septic shock regard severity outcome. enrolled 102 or within 48 h of diagnosis age- gender-matched healthy controls. Irisin was determined upon enrollment all participants week later using an immunoenzymatic method. The outcome recorded 28 days after enrollment. At enrollment, significantly lower than controls (22.3 ± 6.8 μg/L vs. 28.1 6.7 μg/L, p < 0.001), increased 26.6 9.5 0.001). who presented those sepsis, non-survivors survivors both later. However, did not differ between the groups (p > 0.05). Patients higher during first had better Lower independently associated 28-day mortality (sepsis onset: HR 0.44, 95% C.I. 0.26–0.77, = 0.004 after: 0.37, 0.23–0.58, negatively correlated scores, metabolic, inflammatory biomarkers. Circulating decreases early is independent predictor mortality. be promising diagnostic prognostic biomarker; nevertheless, larger studies are needed explore role sepsis.

Language: Английский

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The Emerging Role of FUNDC1-Mediated Mitophagy in Cardiovascular Diseases

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 17, 2021

Mitochondria are highly dynamic organelles and play essential role in ATP synthase, ROS production, innate immunity, apoptosis. quality control is critical for maintaining the cellular function response to stress, growth, differentiation Signals. Damaged or unwanted mitochondria selectively removed by mitophagy, which a crucial determinant of cell viability. Mitochondria-associated Endoplasmic Reticulum Membranes (MAMs) structures that connect ER involved calcium signaling, lipid transfer, mitochondrial dynamic, mitophagy. Abnormal induced mitophagy impairment MAMs dysfunction associated with many diseases, including cardiovascular diseases (CVDs), metabolic syndrome, neurodegenerative diseases. As receptor, FUNDC1 plays pivotal through regulation closely related occurrence several types CVDs. This review covers mechanism FUNDC1-mediated formation, particular focus on its

Language: Английский

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FUNDC1: An Emerging Mitochondrial and MAMs Protein for Mitochondrial Quality Control in Heart Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9151 - 9151

Published: May 23, 2023

Heart diseases (HDs) are the leading cause of mortality worldwide, with mitochondrial dysfunction being a significant factor in their development. The recently discovered mitophagy receptor, FUNDC1, plays critical role regulating homeostasis Mitochondrial Quality Control (MQC) system and contributing to HDs. phosphorylation specific regions FUNDC1 varying levels its expression have been shown diverse effects on cardiac injury. This review presents comprehensive consolidation summary latest evidence regarding MQC system. elucidates association prevalent HDs, such as metabolic cardiomyopathy (MCM), remodeling/heart failure, myocardial ischemia-reperfusion (IR) results indicate that is elevated MCM but reduced instances remodeling, heart IR injury, divergent impacts function among distinct Exercise has identified powerful preventive therapeutic approach for managing Additionally, it suggested exercise-induced enhancement may be attributed AMPK/FUNDC1 pathway.

Language: Английский

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