BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

OBJECTIVETo explore the effects of activating silent information regulator 1 (SIRT1) on early myocardial damage in severely burned rats.

METHODSTwenty-four healthy male SD rats were divided into sham injury group (SI), scald group (S), and resveratrol (RSV) treatment group (RT) according to the random number table, with 8 rats in each group. Rats in groups S and RT were inflicted with 30% TBSA full-thickness scald on the back by immersing in 95 °C water for 18 s. Immediately after injury, rats in group S were intraperitoneally injected with 10 mL normal saline (50 mL/kg) and those in group RT with 10 mL normal saline (50 mL/kg)+10 µL RSV in the concentration of 1 g/mL (50 mg/kg). Backs of rats in group SI were immersed in 20 °C room temperature water for 18 s to simulate the scald process. Heart tissues and aorta abdominalis blood samples were collected at post injury hour (PIH) 6. The histomorphology of heart tissues was observed with HE staining. The serum contents of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined with ELISA. The protein expressions of SIRT1 and caspase-3 and mRNA expressions of SIRT1, caspase-3, IL-1β, and TNF-α in heart tissue specimens were determined with Western blotting and real-time fluorescent quantitative RT-PCR (with protein level denoted as gray value). Data were processed with one-way analysis of variance and LSD- t test.

RESULTS(1) In group SI, myocardial fibers were in irregularly cylindrical shape, neatly arranged, and the transverse striation were distinct. In group S, myocardial interstitial edema, disorder of myocardial fiber arrangement, and cytoplasm destruction were observed. In group RT, the degrees of myocardial interstitial edema, disorder of myocardial fiber arrangement, and cytoplasm destruction were alleviated in comparison with those of group S. (2) The serum contents of CK and LDH of rats in group S were respectively (2 385 ± 712) and (2 551 ± 196) U/L, which were significantly higher than those in the group SI [(290 ± 59) and (759 ± 60) U/L, with t values respectively 9.466 and 25.452, P values below 0.01]. The serum contents of CK and LDH of rats in group RT were respectively (1 336 ± 149) and (2 209 ± 133) U/L, which were significantly lower than those of group S (with t values respectively -4.506 and -4.860, P values below 0.01). (3) The protein expressions of SIRT1 and caspase-3 in heart tissue of rats in group S were respectively 0.47 ± 0.11 and 0.48 ± 0.12, which were significantly higher than those in group SI [0.18 ± 0.06 and 0.09 ± 0.05, with t values respectively 4.813 and 9.014, P values below 0.01]. The protein expression of SIRT1 in heart tissue of rats in group RT was 0.74 ± 0.18, which was significantly higher than that of group S (t = 4.561, P < 0.01); the protein expression of caspase-3 in heart tissue of rats in group RT was 0.21 ± 0.08, which was significantly lower than that of group S (t = -6.239, P < 0.01). (4) The mRNA expressions of SIRT1, caspase-3, IL-1β, and TNF-α in heart tissue of rats in group S were respectively 2.33 ± 0.24, 1.96 ± 0.20, 2.46 ± 0.21, 1.89 ± 0.37, which were significantly higher than those in group SI (1.00 ± 0.07, 1.00 ± 0.06, 1.00 ± 0.08, 1.00 ± 0.09, with t values respectively 14.961, 12.823, 18.559, 6.679, P values below 0.01). The mRNA expression of SIRT1 in heart tissue of rats in group RT was 2.89 ± 0.31, which was significantly higher than that of group S (t = 3.997, P < 0.01). The mRNA expressions of caspase-3, IL-1β, and TNF-α in heart tissue of rats in group RT were respectively 1.31 ± 0.08, 1.64 ± 0.09, 1.25 ± 0.08, which were significantly lower than those of group S (with t values respectively -8.264, -10.245, -4.818, P values below 0.01).

CONCLUSIONSThe expression of SIRT1 in heart tissue is upregulated in the early stage of severely burned rats. Activation of SIRT1 by RSV can alleviate myocardial tissue injury and reduce apoptosis of cardiac myocytes and secretion of IL-1β and TNF-α.

Animals ; Antioxidants ; Apoptosis ; Burns ; Caspase 3 ; genetics ; metabolism ; Edema ; metabolism ; Interleukin-1beta ; Male ; Myocardium ; metabolism ; pathology ; Myocytes, Cardiac ; RNA, Messenger ; genetics ; Rats ; Serum ; Sirtuin 1 ; genetics ; metabolism ; Stilbenes ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Up-Regulation ; physiology

BACKGROUNDSIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear.

METHODSThe effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 µmol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting.

RESULTSOver expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-κB p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-κB p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).

CONCLUSIONSUpregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.

Animals ; Cell Line ; Insulin Resistance ; physiology ; Metformin ; pharmacology ; Muscle Fibers, Skeletal ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Rats ; Sirtuin 3 ; metabolism ; Transcription Factor RelA ; metabolism

OBJECTIVETo observe the changes of mitochondria stress in locus coeruleus and the tyrosine hydroxylasic projection after long-term sleep deprivation.

METHODSSleep deprivation mice model was set up by employing "novel environments" method. The expression of NAD -dependent deacetylase Sirtuin type 3 (SIRT3), which regulates mitochondrial energy production and oxidative stress, and heat shock protein 60 (HSP60), a major biomarker of mitochondrial stress, and the tyrosine hydroxylasic projection from locus coeruleus were analyzed after a 5-day sleep deprivation.

RESULTSCompared to the control group, the expression of SIRT3 in locus coeruleus was significantly decreased in respouse to long-term sleep deprivation, while the expression of HSP60 was significantly increased. In addition, relative to control group, pereentage area of the tyrosine hydroxylasic projection to anterior cingulate cortex was substantial decreased in long-term sleep deprivation group.

CONCLUSIONLong-term sleep deprivation induced the decreased level of SIRT3 expression and the elevation of mitochondrial stress in locus coenileus, which may further lead to the loss of tyrosine hydroxylasic projection in mice.

Animals ; Chaperonin 60 ; metabolism ; Locus Coeruleus ; metabolism ; physiology ; Mice ; Mitochondria ; metabolism ; Mitochondrial Proteins ; metabolism ; Oxidative Stress ; physiology ; Sirtuin 3 ; metabolism ; Sleep Deprivation ; Tyrosine ; metabolism