Sirt3 AND metformin

Acute kidney injury (AKI) is a critical clinical condition that causes kidney fibrosis, and it currently lacks specific treatment options. In this research, we investigate the role of the SENP1-Sirt3 signaling pathway and its correlation with mitochondrial dysfunction in proximal tubular epithelial cells (PTECs) using folic acid (FA) and ischemia-reperfusion-induced (IRI) AKI models. Our findings reveal that Sirt3 SUMOylation site mutation (Sirt3 KR) or pharmacological stimulation (metformin) protected mice against AKI and subsequent kidney inflammation and fibrosis by decreasing the acetylation level of mitochondrial SOD2, reducing mitochondrial reactive oxygen species (mtROS), and subsequently restoring mitochondrial ATP level, reversing mitochondrial morphology and alleviating cell apoptosis...

PURPOSE: We aimed to evaluate whether pulmonary fibrosis occurs in type 2 diabetes rat models and whether VD3 can prevent it by inhibiting pyroptosis. METHODS: Sprague-Dawley rats were assigned to normal control (NC), diabetic model control (MC), low-dose VD3 (LVD), medium-dose VD3 (MVD), high-dose VD3 (HVD) and metformin positive control (PC) groups. Type 2 diabetes model was induced by a high-sugar, high-fat diet combined with STZ injection, and subsequently intervened with VD3 or metformin for 10 weeks...

BACKGROUND AIMS: SLC25A47 was initially identified as mitochondrial hepatocellular carcinoma (HCC)-downregulated carrier protein, but its physiological functions and transport substrates are unknown. We aimed to investigate the physiological role of SLC25A47 in hepatic metabolism. APPROACH RESULTS: Treatment of hepatocytes with metformin found that metformin can transcriptionally activate the expression of Slc25a47, which is required for AMPKα phosphorylation...

Cisplatin is highly effective for killing tumor cells. However, as one of its side effects, ototoxicity limits the clinical application of cisplatin. The mechanisms of cisplatin-induced ototoxicity have not been fully clarified yet. SIRT3 is a deacetylated protein mainly located in mitochondria, which regulates a variety of physiological processes in cells. The role of SIRT3 in cisplatin-induced hair cell injury has not been founded. In this study, primary cultured cochlear explants exposed to 5 μM cisplatin, as well as OC-1 cells exposed to 10 μM cisplatin, were used to establish models of cisplatin-induced ototoxicity in vitro...

BACKGROUND AND OBJECTIVE: PCOS is a common metabolic disorder in women of reproductive age, which pathogenesis is very complex. The role of ferroptosis in PCOS is a novel finding, and the mechanistic studies are not clear. Metformin is a commonly used drug of PCOS but few studies on whether metformin can improve the follicle development and ovarian function in PCOS. We aims to use PCOS mouse model to study the effect of metformin on PCOS based on the ovarian function and explored the regulation of metformin in PCOS mice by intervening in ferroptosis pathway...

Human female fecundity decreases irreversibly as chronological age rises, adversely affecting oocyte quality, consequently worsening pregnancy outcomes and increasing the extent of birth defects. The first-line type 2 diabetes treatment metformin has been associated with delayed aging and reduction of oxidative stress; yet it remains unclear if metformin confers any benefits for oocytes from aged mice, particularly in the context of the assisted human reproductive technology (ART) known as in vitro maturation (IVM)...

Molineria recurvata (MR) has been traditionally used to manage diabetes mellitus in India. However, the molecular mechanism of MR on the diabetic-induced nephropathy has not been clearly investigated. Thus, this study investigates the protective effects of the MR extract on nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was instigated by a single intraperitoneal injection of STZ (45 mg/kg) in male Sprague-Dawley rats. Once the diabetes was successfully induced, the MR extract (200 mg/kg/day) or metformin (200 mg/kg/day) was orally administered for 14 days...

The senescence of vascular smooth muscle cells (VSMCs) is an important cause of cardiovascular disease such as atherosclerosis and hypertension. These senescence may be triggered by many factors, such as oxidative stress, inflammation, DNA damage, and senescence-associated secretory phenotypes (SASPs). Mitochondrial oxidative stress induces cellular senescence, but the mechanisms by which mitochondrial reactive oxygen species (mtROS) regulates cellular senescence are still largely unknown. Here, we investigated the mechanism responsible for the anti-aging effect of metformin by examining links between VSMC senescence and mtROS in in vitro and in vivo...

OBJECTIVES: Endometriosis is a gynecological disease associated with an imbalance between oxidative species production and anti-oxidative defenses. In women, endometriosis has been reported to associate with increased incidence of cardiovascular events. As such, this study aimed to analyze the oxidation-responsive AMPK/SIRT1/PGC-1α/SIRT3 pathway in the heart of a mouse model of endometriosis. The effect of metformin, an insulin-sensitizing and anti-oxidative drug with already shown positive results in endometriotic tissue was studied...

BACKGROUND: High salt intake is the leading dietary risk factor for cardiovascular diseases. Although clinical evidence suggests that high salt intake is associated with nonalcoholic fatty liver disease, which is an independent risk factor for cardiovascular diseases, it remains elusive whether salt-induced hepatic damage leads to the development of cardiovascular diseases. METHODS: Mice were fed with normal or high-salt diet for 8 weeks to determine the effect of salt loading on liver histological changes and blood pressure, and salt withdrawal and metformin treatment were also conducted on some high-salt diet-fed mice...

Sirtuins (SIRT1-7) comprise a family of highly conserved deacetylases with distribution in different subcellular compartments. Sirtuins deacetylate target proteins depending on one common substrate, nicotinamide adenine diphosphate (NAD+ ), thus linking their activities to the status of cellular energy metabolism. Sirtuins had been linked to extending life span and confer beneficial effects in a wide array of immune-metabolic and cardiovascular diseases. SIRT1, SIRT3, and SIRT6 have been shown to provide protective effects in various cardiovascular disease models, by decreasing inflammation, improving metabolic profiles or scavenging oxidative stress...

Osteoporosis is a common metabolic disease that has a high incidence in postmenopausal women. Studies have indicated that oxidative damage plays an important role in the development of postmenopausal osteoporosis. Metformin has been showed to have the ability to relieve excessive oxidation. The aim of the present was to determine the therapeutic effect and potential mechanism of metformin in postmenopausal osteoporosis. Oxidative damage was stimulated in vitro by the addition of H2 O2 to MC3T3-E1 cells and a mouse menopausal model was also constructed...

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease worldwide. Oxidative stress and mitochondrial dysfunction are central to its pathogenesis. Rice husk, the leftover from the milling process, is a good source of phytochemicals with antioxidant activity. This study evaluated the possible protection of purple rice husk extract (PRHE) against diabetic kidney injury. Type 2 diabetic rats were given vehicle, PRHE, metformin, and PRHE+metformin, respectively, while nondiabetic rats received vehicle...

Cancer and diabetes, the two mitochondria-related diseases, have recently been linked to silent mating-type information regulation 2 homolog 3 (SIRT3) activity irregularities. In this study, the effect of metformin, an antidiabetic with anticancer properties, has been evaluated on mitochondrial functionality markers, cell death pathways, and SIRT3 enzyme activity in the colon cancer cell line, HT-29, and human embryonic kidney cells (HEK 293). HT-29 cells were treated with metformin (5, 10, 20, 40, and 80 µM) for 24, 48, and 72 h for measuring the IC50 concentration...

The purpose was to determine the role of AMPK activation in the renal metabolic response to sepsis, the development of sepsis-induced acute kidney injury (AKI) and on survival. In a prospective experimental study, 167 10- to 12-week-old C57BL/6 mice underwent cecal ligation and puncture (CLP) and human proximal tubule epithelial cells (TEC; HK2) were exposed to inflammatory mix (IM), a combination of lipopolysaccharide (LPS) and high mobility group box 1 (HMGB1). Renal/TEC metabolic fitness was assessed by monitoring the expression of drivers of oxidative phosphorylation (OXPHOS), the rates of utilization of OXPHOS/glycolysis in response to metabolic stress, and mitochondrial function by measuring O2 consumption rates (OCR) and the membrane potential (Δψm )...

Diabetes is a metabolic disorder associated with mitochondrial (mt) dysfunction and oxidative stress. The molecular mechanisms involved in diabetes-associated neurological complications remain elusive. This study aims to investigate the protective effect of metformin (MF) on regulatory networks and integrated stress responses in brain tissue of Streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were treated with MF (20 mg/kg BW), and whole brain tissue was harvested for further analysis...

Exposure to arsenic has been linked to the development of type 2 diabetes though its mechanism of toxicity remains unresolved. In this study berberine (BBR) effects on arsenic-induced sirtuin 3 (Sirt3) modifications in isolated mitochondria from rat pancreas were evaluated and compared with metformin (MET). With arsenic, mitochondrial reactive oxygen species (ROS), oxidative stress, and insulin resistance were obtained higher than control. From our results and in the presence of arsenic trioxide, insulin resistance and Sirt3 levels were found to be predominantly elevated that could be the result of compensating mechanisms...

The molecular mechanisms underlying the antineoplastic properties of metformin combined with nelfinavir remain elusive. To explore this question, transmission electron microscopy (TEM) was used to observe the combinatorial effect of inducing autophagosome formation in human cervical cancer cells. Western blotting respectively assayed protein expression of LC3I, LC3II, Beclin-1, Autophagy-related protein 7 (Atg7), Autophagy-related protein 3 (Atg3), NAD-dependent deacetylase sirtuin-3 (SIRT3) and major histocompatibility complex class I chain-related gene A (MICA)...

Mitochondrial damage is involved in the pathogenesis of osteoarthritis. Metformin, one of the most common prescriptions for patients with type 2 diabetes, can reportedly activate Sirtuin 3 (SIRT3) expression which protects mitochondria from oxidative stress. In this study, we investigated the inhibitory property of metformin on mitochondrial damage by focusing on the interleukin-1 beta (IL-1β)-stimulated osteoarthritis model by using primary murine chondrocytes. Our results demonstrated that SIRT3 was downregulated in chondrocytes under IL-1β stimulation, where its expression was positively correlated with mitochondrial damage and reactive oxygen species (ROS) production...

This study investigated the mRNA and protein levels of SIRT1, SIRT3, and SIRT4 in peripheral blood mononuclear cells (PBMCs) from type 2 diabetes patients with retinopathy (diabetic retinopathy (DR) patients) (n = 86) and those without retinopathy (n = 103). The mRNA expression of SIRT1 and SIRT3 was found to be significantly higher in diabetic patients with retinopathy compared to those without retinopathy. Notably, protein levels of SIRT1, SIRT3, and SIRT4 were higher in patients with DR compared with controls after adjusting for diabetes duration and taking metformin (p = ...