Neuregulin-1 Attenuates Myocardial Ischemia/Reperfusion Injury by Activating the UCP2/PINK1/LC3B-mediated Mitophagy DOI Creative Commons

Xin‐Tao Li,

Xinyue Li, Tian Tian

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Abstract BACKGROUND Ischemia/reperfusion (I/R) injury may significantly affect the treatment outcomes and prognosis of patients with acute myocardial infarction following coronary artery recanalization. Available evidence suggests that neuregulin-1 (NRG-1) can provide a protection against I/R is involved in various cardioprotective interventions by potential regulation mitophagy. However, molecular mechanisms linking NRG-1 mitophagy remain to be clarified. This experiment aimed determine whether postconditioning attenuated through explore underlying mechanisms. METHOD Both an vivo model rats vitro hypoxia/reoxygenation (H/R) H9C2 cardiomyocytes were applied. was conducted immediately after or H/R intervention. In experiment, effects determined infarct size, cardiac enzyme histopathologic examinations. The downstream pathways targets screened RNA sequencing Protein-Protein Interaction Networks (PPI). expression levels mitochondrial uncoupling protein 2 (UCP2) mitophagy-related both myocardium measured immunofluorescence staining Western blots. activation observed transmission electron microscopy (TEM) JC-1 staining. RESULTS KEGG GSEA analyses showed enriched treated NRG-1, UCP2 exhibited significant correlation between interaction PINK1. Meanwhile, inhibitor Mdivi-1 eliminated , challenge genipin could also attenuate activating effect on Consistently, using showd up-regulated proteins, activated mitophagy, whereas small interfering (siRNA)-mediated knockdown abolished NRG-1. CONCLUSIONS produce UCP2/PINK1/LC3B signaling pathway.

Language: Английский

AdipoRon ameliorates chronic ethanol induced cardiac necroptosis by reducing ceramide mediated mtROS DOI

Yile Qian,

Yanyu Qi,

Junyi Lin

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Phosphoglycerate mutase 5 exacerbates alcoholic cardiomyopathy in male mice by inducing prohibitin‐2 dephosphorylation and impairing mitochondrial quality control DOI Creative Commons
Jun Tao, Junxiong Qiu, Junmeng Zheng

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: Aug. 1, 2024

The induction of mitochondrial quality control (MQC) mechanisms is essential for the re-establishment homeostasis and cellular bioenergetics during periods stress. Although MQC activation has cardioprotective effects in various cardiovascular diseases, its precise role regulatory alcoholic cardiomyopathy (ACM) remain incompletely understood.

Language: Английский

Citations

7
Astragaloside IV alleviates septic myocardial injury through DUSP1-Prohibitin 2 mediated mitochondrial quality control and ER-autophagy DOI Creative Commons
Junyan Wang,

Xiangyi Pu,

Haowen Zhuang

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Septic cardiomyopathy (SCM) is a complication of myocardial injury in patients with severe sepsis. This study highlights the potential Astragaloside IV(AS) treatment septic and provides reference for developing cardioprotective drugs targeting DUSP1-PHB2-related mitochondria-ER interaction. Dual specificity phosphatase-1 (DUSP1)/Prohibitin 2 cardiomyocyte-specific knockout mice (DUSP1/PHB2CKO) /DUSP1 transgenic (DUSP1/PHB2TG) were used to generate LPS-induced sepsis models. The pathological mechanism by which AS-IV improves heart was detected using cardiac ultrasound, fluorescence staining, transmission electron microscopy, western blotting. After siRNA cardiomyocytes DUSP-1/PHB2, changes mitochondrial function morphology determined qPCR, blotting, ELISA, laser confocal targeted therapeutic effects further examined. SCM leads dysfunction. However, IV (AS) normalizes homeostasis ER function. Notably, protective effect blocked DUSP1/Prohibitin but remained unaffected DUSP1 (DUSP1/PHB2TG). AS DUSP1-PHB2 related

Language: Английский

Citations

5
The UCP2/PINK1/LC3B-mediated Mitophagy is involved in the Protection of NRG1 against Myocardial Ischemia/Reperfusion Injury DOI Creative Commons

Xin‐Tao Li,

Xinyue Li, Tian Tian

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103511 - 103511

Published: Jan. 1, 2025

Language: Английский

Citations

0
Targeting mitochondria by lipid-selenium conjugate drug results in malate/fumarate exhaustion and induces mitophagy-mediated necroptosis suppression DOI Creative Commons

Xing Chang,

Hao Zhou, Jinlin Hu

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(14), P. 5793 - 5811

Published: Oct. 28, 2024

Atherosclerosis (AS) is a chronic vascular disease primarily affecting large and medium-sized arteries involves various complex pathological mechanisms factors. Previous studies have demonstrated close association between atherosclerosis inflammatory damage, metabolic disorders, gut microbiota. It also closely linked to several cellular processes, such as endothelial cell pyroptosis, ferroptosis, mitophagy, mitochondrial dynamics, biogenesis. Mitophagy has been recognized previously unexplored mechanism contributing injury in atherosclerosis. Our study aims further elucidate the potential relationship AS-induced mitophagy dysfunction interaction of TMBIM6 NDUFS4. Data from that AS mice was associated with substantial activation oxidative stress along marked reduction expression increased fission, leading homeostasis disruption. However, under pharmacological intervention, levels significantly increased, fission notably reduced, damage were suppressed, while necroptotic pathways cells blocked. Interestingly, deletion or NDUFS4 animal models lines markedly impaired therapeutic effects drug, disrupting its regulation re-emergence responses damage. Metabolomics analysis revealed autophagy plays pivotal regulatory role during drug intervention after genetic modification The (macroautophagy/mitophagy) alleviated negative induced by lipid cells, likely TMBIM6-NDUFS4 axis. Subsequent gene experiments knocking out negates on lipid-induced function. In summary, our research reveals phenotypic through influenced Pharmacological can restore regulating via pathway. This novel insight suggests may serve key target for

Language: Английский

Citations

1
High-Throughput Screening of an FDA-Approved Compound Library Reveals a Novel GAS6 Receptor Agonist for Therapeutic Intervention in Septic Myocardial and microvascular Injury via Modulation of Danger-Associated Molecular Patterns DOI Creative Commons

Haowen Zhuang,

Chun Guang Li, Lingjun Wang

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(15), P. 6222 - 6240

Published: Nov. 11, 2024

PGAM5 and VDAC1 have both been reported to regulate mitophagy. However, the mechanisms by which they sepsis-induced inflammatory microvascular injury remain unverified. In previous studies, we established role of this regulatory axis in various phenotypic processes, including mitophagy, mitochondrial biogenesis, unfolded protein response, dynamics, while further confirming interactive proteins within axis. validation elucidation these phenotypes primarily focused on ischemic heart diseases such as myocardial failure. Sepsis-related is currently recognized a significant cardiac impairment, although there are cardioprotective nutritional agents available for supportive therapy, fundamental research validating upstream targets still lacking. Based our research, explored mitophagy dysfunction mediated its coronary injury. We also confirmed material basis metabolic pathway regulation targeting PGAM5- mechanism with relevant drugs. Our findings suggest that PGAM5-mediated may be crucial factor leading injury, interacting VDAC1-mediated membrane dysfunction. Animal experiments revealed cardiac-specific knockout could reverse LPS-induced damage, restoring ejection function functionality. vitro studies PGAM5-VDAC1 interaction can normalize normal morphology structure mitochondria maintaining energy metabolism levels respiratory chain function. Further pharmacological indicated active ingredients traditional Chinese medicine-Puerarin (TCM, GAS6 Receptor Agonist) target inhibit necrotic apoptosis cardiomyocytes, potentially reversing pathway-related TCM emerge prospective therapeutic agent

Language: Английский

Citations

1
Neuregulin-1 Attenuates Myocardial Ischemia/Reperfusion Injury by Activating the UCP2/PINK1/LC3B-mediated Mitophagy DOI Creative Commons

Xin‐Tao Li,

Xinyue Li, Tian Tian

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Abstract BACKGROUND Ischemia/reperfusion (I/R) injury may significantly affect the treatment outcomes and prognosis of patients with acute myocardial infarction following coronary artery recanalization. Available evidence suggests that neuregulin-1 (NRG-1) can provide a protection against I/R is involved in various cardioprotective interventions by potential regulation mitophagy. However, molecular mechanisms linking NRG-1 mitophagy remain to be clarified. This experiment aimed determine whether postconditioning attenuated through explore underlying mechanisms. METHOD Both an vivo model rats vitro hypoxia/reoxygenation (H/R) H9C2 cardiomyocytes were applied. was conducted immediately after or H/R intervention. In experiment, effects determined infarct size, cardiac enzyme histopathologic examinations. The downstream pathways targets screened RNA sequencing Protein-Protein Interaction Networks (PPI). expression levels mitochondrial uncoupling protein 2 (UCP2) mitophagy-related both myocardium measured immunofluorescence staining Western blots. activation observed transmission electron microscopy (TEM) JC-1 staining. RESULTS KEGG GSEA analyses showed enriched treated NRG-1, UCP2 exhibited significant correlation between interaction PINK1. Meanwhile, inhibitor Mdivi-1 eliminated , challenge genipin could also attenuate activating effect on Consistently, using showd up-regulated proteins, activated mitophagy, whereas small interfering (siRNA)-mediated knockdown abolished NRG-1. CONCLUSIONS produce UCP2/PINK1/LC3B signaling pathway.

Language: Английский

Citations

0