Browsing by Subject "Mitophagy"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Publication
    Open Access
    Cardiomyoprotective effect of Tanshinone IIA in diabetic cardiomyopathy achieved through enhancing PINK1-Parkin dependent mitophagy
    (2026) Chao Yu; Ping Li; Nannan Li; Ke Wu; Biología Celular e Histología
    This study aimed to explore the beneficial effects and underlying protection mechanism of Tanshinone IIA (TSIIA) in diabetic cardiomyopathy (DCM) from the perspectives of mitophagy and mitochondrial integrity. Here, we found that TSIIA significantly increased STZ-induced body weight (L-TSIIA, 299.5 vs. 276.3; H-TSIIA, 308.3 vs. 276.3) and reduced blood glucose concentration (H-TSIIA, 16.1 vs. 21.5). Meanwhile, TSIIA effectively restored the function and morphology of myocardial tissue in diabetes mellitus (DM) rats. Further, TSIIA has been confirmed to have a protective effect on the ultrastructure and function of myocardial mitochondria, which was achieved through activation of mitophagy, as evidenced by enhanced co-localization of LC3 and COX IV (H-TSIIA, 88188.0 vs. 14829.0). Mechanistically, TSIIA alleviated DCM via activation of the PINK1/Parkin axis, increasing PINK1 (H-TSIIA, 0.5 vs. 0.2), Parkin (H-TSIIA, 0.6 vs. 0.3), Beclin-1 (H-TSIIA, 0.6 vs. 0.2) and LC3II/I (H-TSIIA, 0.5 vs. 0.3) expression, as well as decreasing p62 (H-TSIIA, 1.4 vs. 3.6) expression. This study provided a novel insight into the protective effect of TSIIA in DCM and revealed, for the first time, that TSIIA could noticeably improve STZ-induced DCM by enhancing PINK1-Parkin dependent mitophagy.
  • Thumbnail Image
    Publication
    Open Access
    Cardioprotective mechanisms of Jiangfu Decoction against myocardial ischemia may involve regulation of the AMPK/PINK1/ Parkin mitochondrial autophagy pathway
    (2026) Yiwei Hao; Chen Li; Haoying Li; Xue Han; Hefei Wang; Xi Chu; Zhiwei Su; Shijiang Sun; Yawei Zhao; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    Background. Jiangfu Decoction (JFD) is a classical traditional herbal medicine used to clinically treat ischemic heart disease (IHD). Nonetheless, the influence of JFD on myocardial ischemia (MI), along with its precise underlying mechanism, is still unclear. The objective of this research was to investigate the potential mechanisms by which JFD exerts cardio protective effects on MI induced by isoproterenol (ISO). Methods. An acute MI model was established by subcutaneous injection of ISO (85 mg/kg/d). To evaluate alterations in myocardial structure, electrocardiogram recordings and heart histology examinations were employed. The myocardial ultrastructure was observed by transmission electron microscopy (TEM). Using specific kits, the levels and activities of oxidative stress markers as well as inflammatory cytokines were separately assessed. Western blotting was employed to assess the expression levels of proteins related to adenosine monophosphate activated protein kinase (AMPK), PTEN-induced putative kinase 1 (PINK1), Parkin, Nod-like receptor protein 3 (NLRP3), and Caspase-1. Results. The findings show that JFD treatments markedly diminished heart rate, pathological alterations in cardiac tissue, chondriosome injury, and serum concentrations of creatine kinase, creatine kinasemyocardial band, lactate dehydrogenase, malon dialdehyde, interleukin-1β, and interleukin-18. Concurrently, these treatments augmented the activation of superoxide dismutase, catalase, and glutathione peroxidase in the serum of animals subjected to ISO treatment. Additionally, JFD also reversed the ISO induced changes in the levels of AMPK, PINK1, Parkin, NLRP3, and Caspase-1. Conclusion. JFD exhibits a notable safeguarding influence on MI via a mechanism that involves regulation of the AMPK/PINK1/Parkin mitochondrial autophagy pathway, inhibition of pyroptosis, and reduction of oxidative stress and inflammation.
  • Thumbnail Image
    Publication
    Open Access
    Dynamin-related protein 1 (Drp1) mediating mitophagy contributes to the pathophysiology of nervous system diseases and brain injury
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Wu, Qiong; Luo, Cheng Liang; Tao, Lu Yang
    As the main source of energy (celluar ATP) in eukaryotic cells, mitochondria are involved in cellular physiology and pathology. The balance of mitochondrial dynamic, fission and fusion regulated by quality control mechanisms, provides a guarantee for maintaining mitochondrial function, even celluar function. Worn out mitochondria would be removed through mitophagy which is regulated by autophagy related proteins and mitochondrial membrane proteins. Drp1, dynamicrelated protein 1, is regarded as one of the most important proteins to evaluate mitochondrial fission mediating mitophagy in neurodegenerative diseases (eg. Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis) and heart failure. Recent studies have focused on the roles of Drp1 in ischemia-induced mitophagy in the hippocampal CA3 region, and traumatic brain injury (TBI)-induced cell death together with functional deficits. However, the exact mechanisms have not been well characterized. In this review, we will discuss and clarify the role of Drp1 and mitophagy in nervous system diseases and brain injury therein, with a special emphasis on their molecular mechanisms mediating mitochondrial dynamics and mitophagy
  • Thumbnail Image
    Publication
    Open Access
    Ethanol-induced mitophagy in liver is associated with activation of the PINK1-Parkin pathway triggered by oxidative DNA damage
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Eid, Nabil; Ito, Yuko; Horibe, Akio; Otsuki, Yoshinori
    Mitophagy is a cytoprotective mechanism against mitochondrial damaging agents. Studies demonstrating morphological evidence for the involvement of the PINK1-Parkin pathway in the hepatocyte mitophagic response to ethanol toxicity, and potential links to apoptosis and mitochondrial alterations such as spheroid formation are still lacking. We addressed these unresolved issues using a rat model of binge alcohol exposure. Adult rats were injected with ethanol (5g/kg) and liver samples were taken at 0, 3, 6, and 24 hours after ethanol administration and processed for light and electron microscopic studies. Ethanol induced a low level of hepatocyte apoptosis, peaking at 3 h and decreasing significantly by 24 h. In contrast, there was enhanced formation of mitophagic vacuoles in the majority of normal hepatocytes of ethanol-treated rats (ETRs), which peaked at 6 h and was maintained up to 24 h based on electron microscopy and TUNEL/LC3 double labelling. Moreover, enhanced mitophagy in ETR hepatocytes was confirmed by increased LC3 puncta formation, and co-localization of Parkin and LC3 with mitochondrial and lysosomal markers. Immunoelectron microscopy demonstrated the localization of PINK1 and Parkin to damaged mitochondria of ETR hepatocytes, which was consistent with co-localization of Parkin with 8-OHdG, a marker of oxidative mitochondrial DNA damage. Furthermore, electron microscopy showed enhanced formation of mitochondrial spheroids in ETR hepatocytes. These data are the first direct morphological evidence linking PINK1-Parkin pathway activation to the enhanced mitophagic response of hepatocytes to ethanol toxicity. Ethanol-induced hepatic mitophagy may be a prosurvival mechanism, which may have therapeutic implications.
  • Thumbnail Image
    Publication
    Open Access
    Intermittent fasting-induced autophagy normalization confers hepatic protection in metabolic dysfunction-associated fatty liver disease: Mechanistic insights and implications
    (2026) Gehan El-Akabawy; MoezAlIslam E. Faris; Manoj B. Menon; Mohamed Abdel Wahab; Farida Hussan; Mohd Hazim Bin Zulkaflee; Nabil Eid; Payal Bhatnagar; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver condition that can progress to steatohepatitis, cirrhosis, and even liver cancer. Macroautophagy (hereinafter referred to as autophagy) is a pro-survival mechanism that facilitates the lysosomal clearance of damaged organelles, abnormal proteins, and excess lipids. A growing body of evidence indicates that autophagy dysfunction and reduced autophagic flux play critical roles in the pathogenesis of MAFLD. Therefore, restoring autophagy in MAFLD may help reduce steatosis and prevent disease progression. Intermittent fasting (IF), involving periods of restricted to no food intake alternating with periods of regulated/free eating, has been demonstrated to have beneficial effects on body composition, glucose regulation, lipid profiles, and liver function in studies involving both animal models of MAFLD and human subjects. Studies involving individuals with obesity and MAFLD have shown that Ramadan intermittent fasting (RIF), an Islamic religious practice that involves abstaining from food and water intake from sunrise to sunset over approximately 30 consecutive days, significantly reduces body weight, BMI, fat mass, and inflammatory markers while improving liver function and steatosis. The hepatoprotective effects of RIF are associated with the enhanced expression of autophagy-related genes and the restoration of autophagic flux. This upregulation of autophagy as a result of RIF makes it a potentially promising therapeutic strategy for MAFLD. This review summarizes various forms of IF, the mechanisms of autophagy, and evidence of autophagy dysfunction in MAFLD. It also explores how IF, specifically RIF, may normalize autophagy, reduce hepatic steatosis, and improve liver function in human subjects.
  • Thumbnail Image
    Item
    Open Access
    The mechanism of dexmedetomidine regulation of the HIF-1α/FUNDC1 axis in myocardial ischemia/reperfusion injury
    (2025) Yidan Huang; Zhenfei Hu; Biología Celular e Histología
    Objective. Myocardial ischemia/reperfusion injury (MIRI) is a life-threatening event that typically follows reperfusion therapy for myocardial infarction. Regarding the effects of dexmedetomidine (Dex) in MIRI, we explored its specific mechanism. Methods. The MIRI rat model was treated with Dex, Topotecan [a hypoxia-inducible factor-1α (HIF-1α) inhibitor], and lentiviral-overexpressing FUN14 domain-containing protein 1 (Lv-oe-FUNDC1), with rat heart rate analysis. The pathological damage of rat myocardial tissue was evaluated by hematoxylin-eosin (HE) and Masson staining. Positive expression levels of PTEN-induced kinase 1 (PINK1), Parkin, microtubule-associated protein 1 light chain 3 (LC3) II/I, p62 and Beclin1 proteins, HIF-1α and FUNDC1 messenger RNA (mRNA), and HIF-1α and FUNDC1 were assessed by western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immuno-histochemical staining, respectively. HIF-1α-FUNDC1 binding sites and targeted binding relationships were predicted and verified via databases and dual-luciferase assay. HIF-1α enrichment levels in the FUNDC1 promoter region were evaluated using a ChIP assay. Results. MIRI rats exhibited myocardial injury and severe myocardial dysfunction, with elevated left ventricular diastolic pressure and p62 expression, reduced left ventricular systolic pressure, and maximum rate of change in left ventricular pressure and PINK1, Parkin, LC3 II/I ratio and Beclin-1 protein levels, which were reversed by Dex treatment. MIRI rats had increased HIF-1α and FUNDC1 expression levels, which were further boosted after Dex treatment. Dex promoted mitophagy to ameliorate myocardial injury in MIRI rats via the HIF-1α/FUNDC1 axis. Conclusion. Dex promoted mitophagy by up-regulating HIF-1α to facilitate the transcriptional expression of FUNDC1, thereby ameliorating myo-cardial injury in MIRI rats.