Browsing by Author "Bhaskara, Meghana"

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    Importance of Per2 in cardiac mitochondrial protection during stress
    (Springer Nature, 2024-01-14) Bhaskara, Meghana; Anjorin, Olufisayo; Yoniles, Arris; Liu, Jianyun; Wang, Meijing; Surgery, School of Medicine
    During myocardial injury, inflammatory mediators and oxidative stress significantly increase to impair cardiac mitochondria. Emerging evidence has highlighted interplays between circadian protein-period 2 (Per2) and mitochondrial metabolism. However, besides circadian rhythm regulation, the direct role of Per2 in mitochondrial performance particularly following acute stress, remains unknown. In this study, we aim to determine the importance of Per2 protein's regulatory role in mitochondrial function following exposure to inflammatory cytokine TNFα and oxidative stressor H2O2 in human cardiomyocytes. Global warm ischemia (37 °C) significantly impaired complex I activity with concurrently reduced mitochondrial Per2 in adult mouse hearts. TNFα or H2O2 decreased Per2 protein levels and damaged mitochondrial respiratory function in adult mouse cardiomyocytes. Next, mitochondrial membrane potential ([Formula: see text] M) using JC-1 fluorescence probe and mitochondrial respiration capacity via Seahorse Cell Mito Stress Test were then detected in Per2 or control siRNA transfected AC16 Human Cardiomyocytes (HCM) that were subjected to 2 h-treatment of TNFα (100 ng/ml) or H2O2 (100 μM). After 4 h-treatment, cell death was also measured using Annexin V and propidium iodide apoptosis kit through flow cytometry. We found that knockdown of Per2 enhanced TNFα-induced cell death and TNFα- or H2O2-disrupted [Formula: see text]M, as well as TNFα- or H2O2-impaired mitochondrial respiration function. In conclusion, Per2 knockdown increases likelihood of cell death and mitochondrial dysfunction in human cardiomyocytes exposed to either TNFα or H2O2, supporting the protective role of Per2 in HCM during stress with a focus on mitochondrial function.
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    Mesenchymal Stem Cell-Derived Exosomal microRNAs in Cardiac Regeneration
    (MDPI, 2023-12-11) Bhaskara, Meghana; Anjorin, Olufisayo; Wang, Meijing; Surgery, School of Medicine
    Mesenchymal stem cell (MSC)-based therapy is one of the most promising modalities for cardiac repair. Accumulated evidence suggests that the therapeutic value of MSCs is mainly attributable to exosomes. MSC-derived exosomes (MSC-Exos) replicate the beneficial effects of MSCs by regulating various cellular responses and signaling pathways implicated in cardiac regeneration and repair. miRNAs constitute an important fraction of exosome content and are key contributors to the biological function of MSC-Exo. MSC-Exo carrying specific miRNAs provides anti-apoptotic, anti-inflammatory, anti-fibrotic, and angiogenic effects within the infarcted heart. Studying exosomal miRNAs will provide an important insight into the molecular mechanisms of MSC-Exo in cardiac regeneration and repair. This significant information can help optimize cell-free treatment and overcome the challenges associated with MSC-Exo therapeutic application. In this review, we summarize the characteristics and the potential mechanisms of MSC-derived exosomal miRNAs in cardiac repair and regeneration.