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Foxo3a SirT3

Jianzhang Hu, Tong Kan, Xinying Hu
We aim to investigate how Sirt3 (silent mating type information regulation 2 homolog 3) promoting diabetic corneal epithelial wound healing by regulating mitophagy. The effect of HG(High Glucose, 25 mM D-glucose) on Sirt3 and LC3B(light chain 3 beta)which representing of mitophagy were investigated in TKE2 cells (a murine limbal/corneal epithelium-derived progenitor cell line) and corneal epithelium from C57BL/6J-Ins2Akita (Ins2Akita/+ ) mice using RT-PCR and Western blotting. How overexpression of Sirt3 promoting diabetic corneal epithelial wound healing was investigated with cell migration assay、immunofluorescence、 immunofluorescence colocalization and corneal injury model...
February 19, 2019: Experimental Eye Research
Xue Wang, Qingyu Zeng, Ziming Li, Xiao Yang, Weiliang Xia, Zhiwei Chen
BACKGROUND: Small-cell lung cancer (SCLC), a malignant tumor, is usually widely metastatic when diagnosed. The lack of important therapeutic clinical advances makes it difficult to treat. Previous studies showed that Adjudin had anticancer effects in many other human cancers, and it was synergetic with cisplatin in non-small cell lung cancer. However, the mechanism on SCLC was unclear. METHODS: We investigated the potential mechanism and effect of Adjudin on SCLC both in vitro and in vivo...
February 18, 2019: Thoracic Cancer
M P Valdecantos, P Pérez-Matute, P Prieto-Hontoria, M J Moreno-Aliaga, J A Martínez
The aim of this study was to examine the effects of α-lipoic acid (α-LA) on liver mitochondrial bioenergetics and oxidative status for 8 weeks in normal-healthy animals. A pair-fed group was included to differentiate between α-LA direct effects and those changes due to reduced food intake. α-LA decreased body weight gain, liver weight and insulin levels with no differences compared to its pair-fed group. α-LA significantly reduced energy efficiency, the activity of the electron transport chain complexes and induced a lower efficiency of oxidative phosphorylation with reduced ATP production...
February 15, 2019: International Journal of Food Sciences and Nutrition
Sabrina Chriett, Arkadiusz Dąbek, Martyna Wojtala, Hubert Vidal, Aneta Balcerczyk, Luciano Pirola
Butyrate and R-β-hydroxybutyrate are two related short chain fatty acids naturally found in mammals. Butyrate, produced by enteric butyric bacteria, is present at millimolar concentrations in the gastrointestinal tract and at lower levels in blood; R-β-hydroxybutyrate, the main ketone body, produced by the liver during fasting can reach millimolar concentrations in the circulation. Both molecules have been shown to be histone deacetylase (HDAC) inhibitors, and their administration has been associated to an improved metabolic profile and better cellular oxidative status, with butyrate inducing PGC1α and fatty acid oxidation and R-β-hydroxybutyrate upregulating oxidative stress resistance factors FOXO3A and MT2 in mouse kidney...
January 24, 2019: Scientific Reports
Yonghan Peng, Cheng Yang, Xiaolei Shi, Ling Li, Hao Dong, Changcheng Liu, Ziyu Fang, Zeyu Wang, Shaoxiong Ming, Min Liu, Bin Xie, Xiaofeng Gao, Yinghao Sun
High oxalic acid and calcium oxalate (CaOx)-induced renal tubular epithelial cell (TEC) injury plays a key role in nephrolithiasis. However, the mechanism remains unknown. Gene array analysis of the mice nephrolithiasis model indicated significant downregulation of sirtuin 3 (Sirt3) and activation of mitogen-activated protein kinase (MAPK) pathway. Kidney biopsy tissues of renal calculi patients also showed decreased Sirt3 expression. Silencing Sirt3 exacerbated oxidative stress and TEC death under CaOx stimulation...
January 15, 2019: Cell Death & Disease
Tahereh Farkhondeh, Saeed Samarghandian, Mohsen Azimi-Nezhad
As many individuals worlwide are exposed to arsenic, it is necessary to unravel the role of arsenic in the risk of obesity and diabetes. Therefore, the present study reviewed the effects of arsenic exposure on the risk and potential etiologic mechanisms of obesity and diabetes. It has been suggested that inflammation, oxidative stress, and apoptosis contribute to the pathogenesis of arsenic-induced diabetes and obesity. Though arsenic is known to cause diabetes through different mechanisms, the role of adipose tissue in diabetes is still unclear...
January 22, 2019: Journal of Cellular Physiology
Verónica Martínez-Jiménez, Nancy Cortez-Espinosa, Eduardo Rodríguez-Varela, Mariela Vega-Cárdenas, Margarita Briones-Espinoza, Víctor M Ruíz-Rodríguez, Nallely López-López, Armando Briseño-Medina, Eneida Turiján-Espinoza, Diana P Portales-Pérez
INTRODUCTION: Sirtuins regulate energy metabolism and insulin sensitivity through their ability to act as energy sensors and regulators in several metabolic tissues. AIM: To evaluate the expression levels of sirtuin genes SIRT1, SIRT2, SIRT3 and SIRT6 and their target genes (PPAR-α, PGC1-α, NRF1, DGAT1, PPAR-γ and FOXO3a) in subcutaneous adipose tissue collected from individuals with normoweight, overweight and obesity. METHODS: Adipose tissue samples, obtained by lipoaspiration during liposuction surgery, were processed to obtain RNA, which was reverse-transcribed to cDNA...
January 2019: Diabetes & Metabolic Syndrome
Ziqiang Wang, Ying Li, Ying Wang, Kunxiao Zhao, Yanqing Chi, Baoxing Wang
High glucose(HG)-induced oxidative stress and apoptosis in renal tubular epithelial cells play an important role in the pathogenesis of diabetic nephropathy. Pyrroloquinoline quinine (PQQ), a new B vitamin, has been demonstrated to be important in antioxidant and anti-apoptotic effects. However, its effect on HK-2 cells and the potential mechanism are rarely investigated. In this study, we investigated that PPQ had protective effects against HG-induced oxidative stress damage and apoptosis in vitro model of diabetic nephropathy...
November 28, 2018: Biochemical and Biophysical Research Communications
Yitian Zheng, Binhao Shi, Mengqing Ma, Xiaoqin Wu, Xianhe Lin
Class III histone deacetylases (HDACs) belong to the proteasome family, comprising seven family members identified in mammalian cells, identified Sirt1-Sirt7. As an important member of HDACs, Sirt3 is hotly debated for its multiple functions. It was reported that Sirt3 got involved in the alleviation of multiple diseases, including myocardial infarction, neuron ischemia, hypertrophy, and diabetic myopathy. Through regulating many cellular mechanisms, such as apoptosis, autophagy, and clearance of reactive oxygen species (ROS), Sirt3 played an important role in the alleviation of myocardial ischemia-reperfusion injury...
November 28, 2018: Journal of Cellular Physiology
Jianmei Gao, Yingshu Xu, Jianyong Zhang, Jingshan Shi, Qihai Gong
Lithocarpus polystachyus Rehd. (sweet tea; ST) leaves is a type of Chinese folkloric medicine from southern China. The purpose of the present study was to explore the neuroprotective effect of ST, and to explore its underlying mechanisms in hydrogen peroxide (H2O2)‑induced neuronal cell injury in cultured human neuroblastoma. H2O2 was used as oxidant inducer and human SH‑SY5Y neuroblastoma cells were treated with various concentrations of ST. Cell viability and cell death were detected using MTT and LDH assays, respectively...
October 5, 2018: International Journal of Molecular Medicine
Sai Ma, Jiangwei Chen, Jing Feng, Ran Zhang, Miaomiao Fan, Dong Han, Xiang Li, Congye Li, Jun Ren, Yabin Wang, Feng Cao
The NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome-mediated inflammatory responses are critically involved in the progression of atherosclerosis (AS), which is the essential cause for cardiovascular diseases. Melatonin has anti-inflammatory properties. However, little is known about the potential effects of melatonin in the pathological process of AS. Herein, we demonstrate that melatonin suppressed prolonged NLRP3 inflammasome activation in atherosclerotic lesions by reactive oxygen species (ROS) scavenging via mitophagy in macrophages...
2018: Oxidative Medicine and Cellular Longevity
Jianmei Gao, Shuang Liu, Fan Xu, Yuangui Liu, Chun Lv, Yan Deng, Jingshan Shi, Qihai Gong
Oxidative stress-induced neuronal cell damage is a crucial factor in the pathogenesis of mitochondria-associated neurological diseases. Therefore, elimination of overproduction of mitochondrial reactive oxygen species (mtROS) may be a potential strategy for prevention and treatment of neurological diseases. In the present study, the neuroprotective effects of trilobatin (TLB), a novel small molecule monomer derived from Lithocarpus polystachyus Rehd, and its underlying mechanisms were investigated in vitro using hydrogen peroxide (H2 O2 )-induced oxidative stress model in a neuron-like PC12 cell...
2018: Frontiers in Molecular Neuroscience
Dong-Yang Zhang, Chun-Feng Zhang, Bi-Cheng Fu, Lu Sun, Xue-Qing Wang, Wei Chen, Wei Liu, Kai-Yu Liu, Guo-Qing Du, Chong-Yi Ma, Shu-Lin Jiang, Ren-Ke Li, Hai Tian
Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the possible mechanisms underlying its influence are unknown. We hypothesized that SIRT3 increases the antioxidant capacity of aged cells and improves the efficacy of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in aged patients. In vitro, the antioxidant capacity of old hMSCs (O-hMSCs) was increased after SIRT3 overexpression using a gene transfection technique, while the antioxidant capacity of young hMSCs (Y-hMSCs) was decreased by SIRT3 silencing...
November 2018: Journal of Cellular and Molecular Medicine
Jing-Rong Lin, Yan-Jun Zheng, Ze-Bei Zhang, Wei-Li Shen, Xiao-Dong Li, Tong Wei, Cheng-Chao Ruan, Xiao-Hui Chen, Ding-Liang Zhu, Ping-Jin Gao
Endothelial-to-mesenchymal transition (EndoMT) has recently emerged as a potentially important contributor in promoting fibrosis in chronic kidney disease. However, little is known about the role and molecular basis of its involvement in hypertensive renal injury. Here, we aim to determine the role of SIRT (sirtuin) 3 on EndoMT in hypertensive renal injury and to explore its underlying mechanisms. We found that SIRT3 expression was significantly reduced in Ang II (angiotensin II)-induced hypertensive model, accompanied with induction of EndoMT and increased reactive oxygen species and renal fibrosis...
August 2018: Hypertension
Yu-Ting Wu, Kun-Ting Chi, Yueh-Wen Lan, Jui-Chi Chan, Yi-Shing Ma, Yau-Huei Wei
Upregulation of mitochondrial function and oxidative metabolism is a hallmark in the differentiation of stem cells. However, the mechanism underlying the metabolic reprogramming and upregulation of mitochondrial function during the differentiation of human mesenchymal stem cells (hMSCs) is largely unclear. Sirt3 has emerged as a sensor in regulating mitochondrial function and antioxidant defence system in cellular response to energy demand or environmental stimuli, but its roles in stem cell differentiation have not been fully understood...
July 23, 2018: Free Radical Research
Rong Li, Yizhou Quan, Weiliang Xia
SIRT3, a mitochondrial NAD+ -dependent deacetylase, has been reported to restrain prostate cancer growth both in vitro and in vivo, however, its role in metastatic prostate cancer has not been revealed. In this study, we reported that SIRT3 inhibited the epithelial-mesenchymal transition (EMT) and migration of prostatic cancer cells in vitro and their metastasis in vivo. Consistently, based on analyses of tissue microarray and microarray datasets, lower SIRT3 expression level was correlated with higher prostate cancer Gleason scores, and SIRT3 expression were significantly decreased in metastatic tissues compared with prostate tumor tissues...
March 15, 2018: Experimental Cell Research
Neha Mishra, Sonam Lata, Priyanka Deshmukh, Kajal Kamat, Avadhesha Surolia, Tanushree Banerjee
Cellular stress like ER and oxidative stress are the principle causative agents of various proteinopathies. Multifunctional protein PARK7/DJ-1 provides protection against cellular stress. Recently, insulin/IGF also has emerged as a neuro-protective molecule. However, it is not known whether DJ-1 and insulin/IGF complement each other for cellular protection in response to stress. In this study, we show for the first time, that in human and mouse neuronal cell lines, down regulation of DJ-1 for 48 h leads to compensatory upregulation of insulin/IGF signaling (IIS) pathway genes, namely, insulin receptor, insulin receptor substrate, and Akt under normal physiological conditions as well as in cellular stress conditions...
May 2018: BioFactors
Kaviyarasi Renu, Harishkumar Madhyastha, Radha Madhyastha, Masugi Maruyama, Sankarganesh Arunachlam, Abilash V G
Exposure to arsenic in drinking water can stimulate a diverse number of diseases that originate from impaired lipid metabolism in adipose and glucose metabolism, leading to insulin resistance. Arsenic inhibits differentiation of adipocyte and mediates insulin resistance with diminutive information on arsenicosis on lipid storage and lipolysis. This review focused on different mechanisms and pathways involved in adipogenesis and lipolysis in adipose tissue during arsenic-induced diabetes. Though arsenic is known to cause type2 diabetes through different mechanisms, the role of adipose tissue in causing type2 diabetes is still unclear...
March 1, 2018: Toxicology Letters
Chao Song, Jiamin Zhao, Beibei Fu, Dan Li, Tingchao Mao, Wei Peng, Haibo Wu, Yong Zhang
Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...
November 2017: Free Radical Biology & Medicine
Rashmita Pradhan, Rahul Kumar, Shashank Shekhar, Nitish Rai, Akash Ambashtha, Joyita Banerjee, Mona Pathak, S N Dwivedi, Sharmistha Dey, Aparajit B Dey
BACKGROUND: Ageing process is characterized by a decline in function; different age related diseases and excessive age associated mortality. There has always been a quest for easily accessible biomarkers to monitor and identify the development of age-associated stress for providing new anti-ageing strategies. Forkhead box protein O3A (FOXO3A) and Sirtuin3 (SIRT3) are such potential markers which plays important role in a wide variety of cellular mechanisms and has been proposed to be an ideal candidate to study longevity and are potential candidate for healthy ageing by oxidative burst...
September 2017: Experimental Gerontology
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