Oxidative stress in endothelial cells is pivotal in diabetic retinopathy (DR), with mitochondrial homeostasis being crucial to mitigate this stress. This study explored the roles of mitochondrial sirtuins (SIRTs) in high glucose (HG)-induced oxidative stress, related endothelial impairment, and mitochondrial homeostasis damage in rat retinal microvascular endothelial cells (RMECs). RMECs were cultured under HG or equivalent osmotic conditions. Cell viability was assessed using the Cell Counting Kit-8 assay, whereas cell death and survival were determined via calcein-AM/propidium iodide double staining. Reactive oxygen species (ROS) levels were measured using 2',7'-dichlorofluorescein fluorescence. Expression of mitochondrial SIRTs3-5 and key mitochondrial homeostasis molecules was quantified by the quantitative real-time polymerase chain reaction and confirmed by western blotting. Mitochondrial morphology was evaluated using electron microscopy and the MitoTracker fluorescent probe. A SIRT3-overexpressing RMEC line was constructed to assess the role of SIRT3 in oxidative stress and mitochondrial dynamics. After 48 h of HG exposure, cell viability was significantly reduced, with a concomitant increase in cell death and ROS levels, alongside a marked decrease in SIRT3 expression and molecules associated with mitochondrial dynamics. SIRT3 overexpression reversed these effects, particularly increasing the mitochondrial fusion-related molecule, optic atrophy 1 (OPA1). However, the OPA1 inhibitor, MYLS22, blocked the protective effect of SIRT3, leading to more dead cells, a higher ROS level, and intensified mitochondrial fragmentation. These results suggest that SIRT3 is involved in HG-induced imbalanced mitochondrial dynamics of endothelial cells in DR, potentially through the OPA1 pathway.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.yexcr.2024.114320 | DOI Listing |
J Int Med Res
December 2024
Department of Hepatobiliary Surgery, Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine, Hangzhou, China.
Epithelioid hemangioendothelioma is a low-grade malignant tumor of vascular origin. The rarity of hepatic epithelioid hemangioendothelioma (HEHE) makes the diagnosis and treatment of this entity challenging. We report a case of a 69-year-old female patient who suffered from HEHE and complained of abdominal distension pain with dizziness and appetite loss for more than half a month.
View Article and Find Full Text PDFInflamm Regen
December 2024
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) act together to regulate blood pressure and systemic blood flow by appropriately adjusting blood vessel diameter in response to biochemical or biomechanical stimuli. Ion channels that are expressed in these cells regulate membrane potential and cytosolic Ca concentration ([Ca]) in response to such stimuli. The subsets of these ion channels involved in Ca signaling often form molecular complexes with intracellular molecules via scaffolding proteins.
View Article and Find Full Text PDFMol Med
December 2024
Center for Cancer Immunology, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Metabolic syndrome (MetS) is an indicator and diverse endocrine syndrome that combines different metabolic defects with clinical, physiological, biochemical, and metabolic factors. Obesity, visceral adiposity and abdominal obesity, dyslipidemia, insulin resistance (IR), elevated blood pressure, endothelial dysfunction, and acute or chronic inflammation are the risk factors associated with MetS. Abdominal obesity, a hallmark of MetS, highlights dysfunctional fat tissue and increased risk for cardiovascular disease and diabetes.
View Article and Find Full Text PDFCommun Biol
December 2024
Department of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China.
Cardiovascular diseases (CVDs) and cerebrovascular diseases (CeVDs) are closely related vascular diseases, sharing common cardiometabolic risk factors (RFs). Although pleiotropic genetic variants of these two diseases have been reported, their underlying pathological mechanisms are still unclear. Leveraging GWAS summary data and using genetic correlation, pleiotropic variants identification, and colocalization analyses, we identified 11 colocalized loci for CVDs-CeVDs-BP (blood pressure), CVDs-CeVDs-LIP (lipid traits), and CVDs-CeVDs-cIMT (carotid intima-media thickness) triplets.
View Article and Find Full Text PDFSci Rep
December 2024
Cell and Developmental Biology Laboratory, Research and Development Cell, PIMSR, Parul University, Vadodara, Gujarat, 391760, India.
The SARS-CoV-2 virus that resulted in the COVID-19 pandemic has been implicated in a range of neurological issues, such as encephalopathy, stroke, and cognitive decline. Although the precise mechanism causing these issues is unknown, mounting evidence shows that blood-brain barrier (BBB) disruption is probable2 a major factor. The integrity of the blood-brain barrier (BBB), a highly selective barrier that divides the brain from the systemic circulation, is crucial for preserving normal brain function.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!