Browsing by Subject "Mitochondrial function"

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    Ferritin heavy chain as main mediator of preventive effect of metformin against mitochondrial damage induced by doxorubicin in cardiomyocytes
    (2014-02) Asensio Lopez, Maria del Carmen; Sanchez Mas, Jesus; Pascual Figal, Domingo A.; de la Torre, Carlos; Valdes, Mariano; Lax Pérez, Antonio Manuel; Medicina
    The efficacy of doxorubicin (DOX) as an antitumor agent is greatly limited by the induction of cardiomyopathy, which results from mitochondrial dysfunction and iron-catalyzed oxidative stress in the cardiomyocyte. Metformin (MET) has been seen to have a protective effect against the oxidative stress induced by DOX in cardiomyocytes through its modulation of ferritin heavy chain (FHC), the main iron-storage protein. This study aimed to assess the involvement of FHC as a pivotal molecule in the mitochondrial protection offered by MET against DOX cardiotoxicity. The addition of DOX to adult mouse cardiomyocytes (HL-1 cell line) increased the cytosolic and mitochondrial free iron pools in a time-dependent manner. Simultaneously, DOX inhibited complex I activity and ATP generation and induced the loss of mitochondrial membrane potential. The mitochondrial dysfunction induced by DOX was associated with the release of cytochrome c to the cytosol, the activation of caspase 3, and DNA fragmentation. The loss of iron homeostasis, mitochondrial dysfunction, and apoptosis induced by DOX were prevented by treatment with MET 24h before the addition of DOX. The involvement of FHC and NF-κB was determined through siRNA-mediated knockdown. Interestingly, the presilencing of FHC or NF-κB with specific siRNAs blocked the protective effect induced by MET against DOX cardiotoxicity. These findings were confirmed in isolated primary neonatal rat cardiomyocytes. In conclusion, these results deepen our knowledge of the protective action of MET against DOX-induced cardiotoxicity and suggest that therapeutic strategies based on FHC modulation could protect cardiomyocytes from the mitochondrial damage induced by DOX by restoring iron homeostasis
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    SLMO2 inhibits apoptosis in ovarian cancer cells by modulating mitochondrial function via TRIAP1
    (2026) Yuesong Wang; Zixuan Li; Tianmei Zhang; Yaqi Wang; Biología Celular e Histología
    Objective. This study aimed to investigate the role of SLMO2 in regulating mitochondrial function and its interaction with TRIAP1, which inhibited apoptosis in ovarian cancer cells. The findings provided valuable insights into potential therapeutic targets for ovarian cancer. Methods. Lentiviral infection models were developed using SKOV3 and OVCAR3 ovarian cancer cell lines. Techniques such as flow cytometry, western blotting, immunofluorescence, and transmission electron microscopy were employed to systematically assess the regulatory effects of SLMO2 and TRIAP1 on cell proliferation, apoptosis, mitochondrial function, and autophagy. Additionally, a subcutaneous mouse tumor xenograft model was utilized to further investigate the combined effects of SLMO2 and TRIAP1 on ovarian cancer cells, with the aim of elucidating the specific mechanisms underlying tumor growth and apoptosis. Results. SLMO2 enhanced mitochondrial function by increasing membrane potential and reducing reactive oxygen species (ROS) levels. Furthermore, through its interaction with TRIAP1, SLMO2 inhibited autophagy, which further suppressed apoptosis in ovarian cancer cells and regulated mitochondrial function. In vivo experiments showed decreased ROS levels and reduced expression of autophagy-related proteins, further supporting the roles of SLMO2 and TRIAP1 in the regulation of mitochondrial function. Conclusions. SLMO2 regulated mitochondrial function and inhibited apoptosis in ovarian cancer cells by interacting with TRIAP1. The combination of SLMO2 and TRIAP1 promoted tumor cell growth and induced oxidative stress, suggesting potential therapeutic targets for ovarian cancer.