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Pan-Ke Cheng, Xiao-Long Chen, Xing-Xing Su, Xue-Jiao Su, Chun-Li Hou
Refractory ischemic ulcers that occur in patients with diabetes present a major clinical challenge. Embryonic artery cluster of differentiation 133+ cells (EACCs) may promote the healing of diabetic ulcers; however, the high glucose environment in the diabetic ulcers decreases the survival rate of transplanted EACCs and inhibit their biological function. Furthermore, microcirculation in diabetic ischemic ulcers is impaired, which inhibits the beneficial effect of EACCs. In the current study, the Sirt1 agonist SRT1720 was selected as a therapeutic drug and loaded into a dressing composed of PLGA, collagen and silk (PCSS) formed using electrospinning technology...
June 2018: Experimental and Therapeutic Medicine
Bailin Niu, Kun He, Peizhi Li, Jianping Gong, Xiwen Zhu, Shangmin Ye, Zhibing Ou, Guosheng Ren
Sirtuin 1 (SIRT1) is an NAD(+)‑dependent deacetylase, and a critical regulator in various metabolic processes, such as non‑alcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether activating SIRT1 could modulate the CD36 and nuclear factor (NF)‑κB pathways to protect against liver injury induced by a high‑fat diet (HFD) in mice. A mouse NAFLD model was established by administration of a HFD for 8 weeks. During the last 4 weeks, SRT1720, a specific SIRT1 activator, was added daily to the HFD feed...
May 29, 2018: Molecular Medicine Reports
Antoinette Bugyei-Twum, Christopher Ford, Robert Civitarese, Jessica Seegobin, Suzanne L Advani, Jean-Francois Desjardins, Golam Kabir, Yanling Zhang, Melissa Mitchell, Jennifer Switzer, Kerri Thai, Vanessa Shen, Armin Abadeh, Krishna K Singh, Filio Billia, Andrew A Advani, Richard E Gilbert, Kim A Connelly
Aims: Transforming growth factor β1 (TGF-β1) is a prosclerotic cytokine involved in cardiac remodeling leading to heart failure (HF). Acetylation/de-acetylation of specific lysine residues in Smad2/3 has been shown to regulate TGF-β signaling by altering its transcriptional activity. Recently, the lysine de-acetylase sirtuin 1 (SIRT1) has been shown to have a cardioprotective effect; however SIRT1 expression and activity are paradoxically reduced in HF. Here, we investigate whether pharmacological activation of SIRT1 would induce cardioprotection in a pressure overload model and assess the impact of SIRT1 activation on TGF-β signaling and the fibrotic response...
May 25, 2018: Cardiovascular Research
Kaipeng Huang, Ruiming Li, Wentao Wei
Mesangial proliferative glomerulonephritis (MsPGN) is characterized by glomerular mesangial cells proliferation and extracellular matrix deposition in mesangial area, which develop into glomerulosclerosis. Both silent information regulator 2-related protein 1 (Sirt1) and nuclear factor erythroid 2-related factor 2/ anti-oxidant response element (Nrf2/ARE) pathway had remarkable renoprotective effects. However, whether Sirt1 and Nrf2/ARE pathway can regulate the pathological process of MsPGN remains unknown...
May 18, 2018: European Journal of Pharmacology
Qingling Yang, Shanjun Dai, Xiaoyan Luo, Jing Zhu, Fangyuan Li, Jinhao Liu, Guidong Yao, Yingpu Sun
The quality of postovulatory metaphase II oocytes undergoes a time-dependent deterioration as a result of the aging process. Melatonin is considered an anti-aging agent. However, the underlying mechanisms of how melatonin improves the quality of postovulatory aged oocytes remain largely unclear. In this study, by using mouse model, we found that there were elevated ROS levels and impaired mitochondrial function demonstrated by reduced mitochondrial membrane potential (ΔΨm) and increased mitochondrial aggregation in oocytes aged 24 h, accompanied by an increased number of meiotic errors, unregulated autophagy-related proteins and early apoptosis, which led to decreased oocyte quality and disrupted developmental competence...
May 11, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Long The Nguyen, Hui Chen, Crystal Mak, Amgad Zaky, Carol Pollock, Sonia Saad
Recent studies indicate that SIRT1, an important metabolic sensor and regulator of lifespan, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high-fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (SRT, 25mg/kg/2days i...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Min Jo Kim, Hye Jin An, Dae Hyun Kim, Bonggi Lee, Hye Jin Lee, Sultan Ullah, Su Jeong Kim, Hyoung Oh Jeong, Kyoung Mi Moon, Eun Kyeong Lee, Jungho Yang, Jinia Akter, Pusoon Chun, Hyung Ryong Moon, Hae Young Chung
The NAD+ -dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndromes, such as type 2 diabetes, is a well-known longevity-related gene. Several in vitro and in vivo studies have shown the known protective effects of SIRT1 activators, such as resveratrol and SRT1720, on diabetes- or obesity-induced fatty liver and insulin resistance. Here, we newly synthesized 18 benzoxazole hydrochloride derivatives based on the structure of resveratrol and SRT1720. We performed an in vitro SIRT1 activity assay to identify the strongest SIRT1 activator...
February 15, 2018: Bioorganic & Medicinal Chemistry Letters
Weijin Zhang, Yaoyuan Zhang, Xiaohua Guo, Zhenhua Zeng, Jie Wu, Yanan Liu, Jing He, Ruiting Wang, Qiaobing Huang, Zhongqing Chen
Sepsis is a threatening health problem and characterized by microvascular dysfunction. In this study, we verified that LPS caused the downregulation of Sirt1 and the hyperpermeability of endothelial cells. Inhibition of Sirt1 with ex527 or Sirt1 siRNA displayed a higher permeability, while activation of Sirt1 with SRT1720 reversed the LPS-induced hyperpermeability, formation of fiber stress, and disruption of VE-cadherin distribution. In pulmonary microvascular vein endothelial cells isolated from wild-type mice, Sirt1 was attenuated upon LPS, while Sirt1 was preserved in a receptor of advanced glycation end product-knockout mice...
2017: Oxidative Medicine and Cellular Longevity
Junxiang Ma, Dongmei Song, Yuanyuan Zhang, Li Chen, Shixuan Zhang, Jiaxin Jia, Tian Chen, Caixia Guo, Lin Tian, Ai Gao, Piye Niu
Tertiary butyl alcohol (TBA) is a principal metabolite of methyl tertiary-butyl ether (MTBE), a common pollutant worldwide in the ground or underground water, which is found to produce nervous system damage. Nevertheless, few data regarding the effects of TBA has been reported. Studies indicated that oxidative stress plays a pivotal role in MTBE neurotoxic mechanism. Sirtuin 1 (SIRT1) has been reported to exert a neuroprotective effect on various neurologic diseases via resistance to oxidative stress by deacetylating its substrates...
February 2018: Environmental Toxicology
Adam Khader, Weng-Lang Yang, Laura W Hansen, Salil R Rajayer, Jose M Prince, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
BACKGROUND: Sepsis affects 800,000 patients in the United States annually with a mortality rate of up to 30%. Recent studies suggest that sepsis-associated metabolic derangements due to hypoxic tissue injury, impaired oxygen utilization, and mitochondrial dysfunction contribute to mortality. Sirtuin 1 (Sirt1) is a crucial modulator of energy metabolism during starvation states and has anti-inflammatory effects. Here, we hypothesized that SRT1720, a Sirt1 activator, could attenuate the severity of sepsis...
November 2017: Journal of Surgical Research
Arne Björn Potthast, Theresa Heuer, Simone Johanna Warneke, Anibh Martin Das
BACKGROUND: Sirtuins are NAD+ dependent deacetylases, which regulate mitochondrial energy metabolism as well as cellular response to stress. The NAD/NADH-system plays a crucial role in oxidative phosphorylation linking sirtuins and the mitochondrial respiratory chain. Furthermore, sirtuins are able to directly deacetylate and activate different complexes of the respiratory chain. This prompted us to analyse sirtuin levels in skin fibroblasts from patients with cytochrome c-oxidase (COX) deficiency and to test the impact of different pharmaceutical activators of sirtuins (SRT1720, paeonol) to modulate sirtuins and possibly respiratory chain enzymes in patient cells in vitro...
2017: PloS One
Tetsu Kawabata, Haruhiko Tokuda, Kazuhiko Fujita, Shingo Kainuma, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, Takanobu Otsuka
BACKGROUND/AIMS: Resveratrol is a polyphenol enriched in the skins of grapes and berries, that shows various beneficial effects for human health. In the present study, we investigated the mechanism behind the epidermal growth factor (EGF)-induced migration of osteoblast-like MC3T3-E1 cells, and the effect of resveratrol on this cell migration. METHODS: The cell migration was examined using Boyden chamber, and phosphorylation of each kinase was analyzed by Western blotting...
2017: Cellular Physiology and Biochemistry
Kayvan Zainabadi, Cassie J Liu, Alison L M Caldwell, Leonard Guarente
Overexpression or pharmacological activation of SIRT1 has been shown to extend the lifespan of mice and protect against aging-related diseases. Here we show that pharmacological activation of SIRT1 protects in two models of osteoporosis. Ovariectomized female mice and aged male mice, models for post-menopausal and aging-related osteoporosis, respectively, show significant improvements in bone mass upon treatment with SIRT1 agonist, SRT1720. Further, we find that calorie restriction (CR) results in a two-fold upregulation of sirt1 mRNA expression in bone tissue that is associated with increased bone mass in CR mice...
2017: PloS One
Kuo Du, Anup Ramachandran, Mitchell R McGill, Abdellah Mansouri, Tarik Asselah, Anwar Farhood, Benjamin L Woolbright, Wen-Xing Ding, Hartmut Jaeschke
Mitochondrial biogenesis (MB) is an adaptive response to maintain metabolic homeostasis after mitochondrial dysfunction. Induction of MB during APAP hepatotoxicity has not been studied. To investigate this, mice were treated with toxic doses of APAP and euthanized between 0 and 96 h. At early time points, APAP caused both mitochondrial dysfunction and reduction of mitochondrial mass, indicated by reduced activity of electron transport chain (ETC) complexes I and IV and depletion of mitochondrial DNA (mtDNA), respectively...
October 2017: Food and Chemical Toxicology
Yan Dai, Tyngwei Chen, Heba Ijaz, Elizabeth H Cho, Martin H Steinberg
High fetal hemoglobin (HbF, α2 γ2 ) levels ameliorate the clinical manifestations of sickle cell disease and β thalassemia. The mechanisms that repress HbF expression and silence γ-globin genes in adults are incompletely characterized and only a single HbF inducer, hydroxyurea, is approved for treatment, and only in patients with sickle cell disease. We identified SIRT1, a protein deacetylase, as a new inducer of γ-globin. SIRT1 knockdown decreased, while SIRT1 ectopic expression upregulated γ-globin gene (HBG) expression in primary human erythroid cells and in K562 cells...
November 2017: American Journal of Hematology
Jian Bo, Xiaojuan Wang, Jie Li, Wenqing Wang, Jinqian Zhang
Patients with chronic HBV infection have been reported to suffer a significantly increased risk of NHL, but the underlying mechanisms remain to be clearly explained. The aim of the present study was to clarify the relationship between chronic HBV infection and NHL development. Fluorescence-activated cell sorting, Annexin V/7-aminoactinomycin D staining and MTS assay were used to analyze the rate of apoptosis and cell viability. In addition, western blotting was used to detect protein expression. The effects of the activator of SIRT1, SRT1720, and the inhibitor of SIRT1, nicotinamide, were also analyzed...
July 2017: Oncology Letters
Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F Ceylan, Wei Guo, Jian Yang, Yingmei Zhang
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca(2+) properties were evaluated using echocardiography, IonOptix(®) edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot...
October 2017: Aging Cell
Kazuhiko Fujita, Haruhiko Tokuda, Shingo Kainuma, Gen Kuroyanagi, Naohiro Yamamoto, Rie Matsushima-Nishiwaki, Atsushi Harada, Osamu Kozawa, Takanobu Otsuka
Resveratrol, a polyphenolic compound that is present in grape skins, berries and red wine, may be beneficial for human health through its anti‑inflammatory and anti‑oxidant effects. It has been previously demonstrated that resveratrol exerts its biological effects primarily via sirtuin 1 (SIRT1) activation. We previously reported that triiodothyronine (T3) induces osteocalcin synthesis in osteoblast‑like MC3T3‑E1 cells, and that p38 mitogen‑activated protein (MAP) kinase mediates the T3‑stimulated synthesis of osteocalcin...
September 2017: Molecular Medicine Reports
Yulong Chen, Huanhuan Liu, Xinhong Wang, Hongmei Zhang, Enqi Liu, Xingli Su
Sirtuin 1 (Sirt1) is a longevity gene that has protective effects in cardiovascular diseases (CVDs). The endothelin type A (ETA) receptor is involved in pathogenesis of CVDs. The extracellular signal related kinases 1 and 2 (ERK1/2) signaling pathway is involved in regulation of the ETA receptor induced by some CVD risk factors in vascular smooth muscle cells (VSMCs). Hyperhomocysteinemia (HHcy) is an independent risk factor for CVDs. The present study was designed to investigate the hypothesis that homocysteine up-regulates ETA receptor through the Sirt1/ERK1/2 signaling pathway...
June 1, 2017: Microvascular Research
Linxi Yu, Xiaoxin Liu, Zihang Yuan, Xiaojiaoyang Li, Hang Yang, Ziqiao Yuan, Lixin Sun, Luyong Zhang, Zhengzhou Jiang
Intrahepatic cholestasis is a kind of clinical syndrome along with hepatotoxicity which caused by intrahepatic and systemic accumulations of bile acid. There are several crucial generating factors of the pathogenesis of cholestasis, such as inflammation, dysregulation of bile acid transporters and oxidative stress. SIRT1 is regarded as a class III histone deacetylase (HDAC). According to a set of researches, SIRT1 is one of the most important factors which can regulate the hepatic bile acid metabolism. SRT1720 is a kind of activator of SIRT1 which is 1000 times more potent than resveratrol, and this paper is aimed to study its protective influence on hepatotoxicity and cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in mice...
2017: Frontiers in Pharmacology
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