Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 1, 2024

Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, inflammation. Accumulating evidence has shown that implicated in diseases, such as cancers, cardiac diseases cardiovascular neurological disorders, kidney motor system metabolic disorders. Examining the upstream modulators co-activated partners identifying critical biological events modulated by downstream effectors contribute to presentation elaborate network PGC-1s. Furthermore, discussing correlation between well summarizing therapy targeting helps make individualized precise intervention methods. In this review, we summarize basic knowledge regarding molecular regulatory network, discuss physio-pathological roles human review application PGC-1s, diagnostic prognostic value several therapies pre-clinical studies, suggest directions for future investigations. This presents immense potential treatment hopefully facilitates promotion new therapeutic targets.

Language: Английский

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New Insights into Mitochondria in Health and Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9975 - 9975

Published: Sept. 16, 2024

Mitochondria are a unique type of semi-autonomous organelle within the cell that carry out essential functions crucial for cell's survival and well-being. They location where eukaryotic cells energy metabolism. Aside from producing majority ATP through oxidative phosphorylation, which provides cellular functions, mitochondria also participate in other metabolic processes cell, such as electron transport chain, citric acid cycle, β-oxidation fatty acids. Furthermore, regulate production elimination ROS, synthesis nucleotides amino acids, balance calcium ions, process death. Therefore, it is widely accepted mitochondrial dysfunction factor causes or contributes to development advancement various diseases. These include common systemic diseases, aging, diabetes, Parkinson's disease, cancer, well rare disorders, like Kearns-Sayre syndrome, Leigh myopathy. This overview outlines mechanisms by involved numerous illnesses physiological activities. Additionally, new discoveries regarding involvement both disorders maintenance good health.

Language: Английский

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Macrod1 suppresses diabetic cardiomyopathy via regulating PARP1-NAD+-SIRT3 pathway

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(6), P. 1175 - 1188

Published: March 8, 2024

Language: Английский

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USP7 Promotes Cardiometabolic Disorders and Mitochondrial Homeostasis Dysfunction in Diabetic Mice via stabilizing PGC1β

Pharmacological Research, Journal Year: 2024, Volume and Issue: 205, P. 107235 - 107235

Published: May 28, 2024

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and characterized by left ventricular dysfunction. Currently, there lack effective treatments for DCM. Ubiquitin-specific protease 7 (USP7) plays key role in various diseases. However, whether USP7 involved DCM has not been established. In this study, we demonstrated that was upregulated diabetic mouse hearts NMCMs co-treated with HG+PA or H9c2 cells treated PA. Abnormalities heart morphology function were reversed silencing through conditional gene knockout chemical inhibition. Proteomic analysis coupled biochemical validation confirmed PCG1β one the direct protein substrates aggravated myocardial damage coactivation PPARα signaling pathway. restored expression fatty acid metabolism-related proteins mitochondrial homeostasis inhibiting fission promoting fusion events. Similar effects also observed vitro. Our data promoted cardiometabolic metabolism disorders dysfunction via stabilizing suggested may be therapeutic strategy

Language: Английский

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Super-enhancer-driven LncRNA PPARα-seRNA exacerbates glucolipid metabolism and diabetic cardiomyopathy via recruiting KDM4B

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 86, P. 101978 - 101978

Published: June 29, 2024

Aberrant glucolipid metabolism in the heart is a characteristic factor diabetic cardiomyopathy (DbCM). Super-enhancers-driven noncoding RNAs (seRNAs) are emerging as powerful regulators progression of cardiac diseases. However, functions seRNAs DbCM have not been fully elucidated.

Language: Английский

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ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2

Nutrition and Diabetes, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 22, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of type 2 diabetes mellitus (DM). The transcription factor zinc fingers and homeoboxes (ZHX2) has been implicated in the pathogenesis chronic diseases, yet its precise role underlying mechanism DM-induced hepatic injury remain poorly elucidated. To investigate this, we used high-fat diet (HFD) streptozotocin (STZ) administration to create DM model mice, while high glucose (HG) exposure was simulate vitro. Through various experiments such as luciferase reporter assay, chromatin immunoprecipitation, RNA rescue experiments, aimed uncover mechanisms involving ZHX2. Our findings revealed that ZHX2 lower YTHDF2 higher livers mice HG-induced Huh7 cells. overexpression rescued injury. also reversed ferroptosis vivo Mechanistically, recognized m6A-modified mRNA promoted degradation. In turn, inhibited by binding promoter region. Knockdown led increased cells through activating YTHDF2-induced GPX4 SLC7A11 These highlight involvement ZHX2-YTHDF2-ferroptosis pathway suggest targeting this may hold therapeutic potential for improving injuries.

Language: Английский

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FNDC4 Prevents Aging-Related Cardiac Dysfunction

JACC Basic to Translational Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Cholesterol 25-hydroxylase prevents type 2 diabetes mellitus induced cardiomyopathy by alleviating cardiac lipotoxicity

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(5), P. 167158 - 167158

Published: April 6, 2024

Language: Английский

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PRDM16 Suppresses Ferroptosis to Protect against Sepsis-associated Acute Kidney Injury by Targeting the NRF2/GPX4 Axis

Redox Biology, Journal Year: 2024, Volume and Issue: 78, P. 103417 - 103417

Published: Nov. 7, 2024

Acute kidney injury (AKI) constitutes a significant public health issue. Sepsis accounts for over 50 % of AKI cases in the ICU. Recent findings from our research indicated that PRD1-BF1-RIZ1 homeodomain protein 16 (PRDM16) inhibited progression diabetic disease (DKD). However, its precise role and regulatory mechanism sepsis-induced remain obscure. This study reveals lipopolysaccharide (LPS) cecum ligation puncture (CLP) instigated PRDM16 expression Boston University mouse proximal tubule (BUMPT) cells kidneys, respectively. Functionally, curtailed LPS-induced ferroptosis. Mechanistically, associates with promoter regions nuclear factor-erythroid 2-related factor-2 (NRF2) augments expression, subsequently enhancing glutathione peroxidase 4 (GPX4) expression. Additionally, directly engages GPX4, stimulating Notably, these observations were corroborated human renal tubular epithelial (HK-2) cells. Furthermore, ablation tubules mice NRF2 GPX4 leading to decreased (GSH)/oxidized (GSSG) ratio, increased Fe2+ reactive oxygen species (ROS) production, exacerbated ferroptosis, progression. Conversely, knock-in exhibited opposite effects. Ultimately, adenovirus (ADV)-PRDM16 plasmid or poly (lactide-glycolide acid) (PLGA)-encapsulated formononetin not only mitigated but also alleviated liver, cardiac, lung injury. In summary, inhibits ferroptosis via NRF2/GPX4 axis prevent multi-organ injury, including AKI. PLGA-encapsulated presents promising therapeutic approach.

Language: Английский

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Unravelling the function of prdm16 in human tumours: A comparative analysis of haematologic and solid tumours

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117281 - 117281

Published: Aug. 12, 2024

Extensive research has shown that PR domain 16 (PRDM16) plays a critical role in adipose tissue metabolism, including processes such as browning and thermogenesis of adipocytes, beigeing adipogenic differentiation myoblasts. These functions have been associated with diseases obesity diabetes. Additionally, PRDM16 correlated various other conditions, migraines, heterochromatin abnormalities, metabolic syndrome, cardiomyopathy, sarcopenia, nonsyndromic cleft lip, essential hypertension, among others. However, there is currently no systematic or comprehensive conclusion regarding the mechanism human tumours, haematologic solid tumours. The aim this review to provide an overview progress on tumours by incorporating recent literature findings. Furthermore, we explore prospects precise diagnosis treatment

Language: Английский

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