The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Jun Liu - One of the best experts on this subject based on the ideXlab platform.
-
Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway
Elsevier, 2019Co-Authors: Tao Liu, Tianxiang Ouyang, Huiping Chen, Yan Xiao, Yingying Huang, Jun LiuAbstract:Keloids exhibit cancer-like properties without spontaneous regression and usually recur post excision. Although photodynamic therapy (PDT) is a promising treatment, details of the mechanisms remain to be elucidated. In this study, we investigated mechanisms involved in 5-Aminolevulinic Acid (5-ALA)–based PDT against keloid. Found that 5-ALA-PDT induced superoxide anion-dependent autophagic cell death. Application of autophagy inhibitor 3-Methyladenine (3-MA) significantly prevented the effect that 5-ALA-PDT induced keloid–derived fibroblasts death, but Z-VAK-FMK (apoptotic inhibitor) did not. Interestingly, 5-ALA-PDT promoted the SIRT3 protein expression and the activity of mitochondrial superoxide dismutase 2 (SOD2), but SIRT1 protein expression level was decreased. SOD2 as a key enzyme can decrease mitochondrial ROS (mROS) level, Deacetylation of SOD2 by SIRT3 regulates SOD2 enzymatic activity has been identified. Then we explored SOD2 acetylation level with immunoprecipitation, found that 5-ALA-PDT significantly increased the acetylation levels of SOD2. In order to confirm deacetylation of SOD2 regulated by SIRT3, 3-TYP (SIRT3 inhibitor) was used. Found that inhibition of SIRT3 by 3-TYP significantly increased the level of SOD2 acetylation level compared with control group or 5-ALA-PDT group. To explore the connection of SIRT1 and SIRT3, cells were treated with EX527(SIRT1 inhibitor) or SRT1720 (SIRT1 activator), and EX527 increased SIRT3 protein level, however, SRT1720 displayed the opposite effect in the present or absence of 5-ALA-PDT. Moreover SIRT1-inhibited cells are more resistant to 5-ALA-PDT and showing decreased ROS accumulation. These results may demonstrate that 5-ALA-PDT induced SIRT1 protein level decreased, which promoted the effect of SIRT3 increased activity of SOD2 that can reduce mROS level, and then compromised 5-ALA-PDT induced autophagic cell death. Keywords: Keloid, 5-aminolevulinic acid, SIRT1, SIRT3, Autophag
-
efficacy of 5 aminolevulinic acid based photodynamic therapy against keloid compromised by downregulation of sirt1 sirt3 sod2 mros dependent autophagy pathway
Redox biology, 2019Co-Authors: Tao Liu, Tianxiang Ouyang, Huiping Chen, Yan Xiao, Yingying Huang, Jun LiuAbstract:Keloids exhibit cancer-like properties without spontaneous regression and usually recur post excision. Although photodynamic therapy (PDT) is a promising treatment, details of the mechanisms remain to be elucidated. In this study, we investigated mechanisms involved in 5-Aminolevulinic Acid (5-ALA)-based PDT against keloid. Found that 5-ALA-PDT induced superoxide anion-dependent autophagic cell death. Application of autophagy inhibitor 3-Methyladenine (3-MA) significantly prevented the effect that 5-ALA-PDT induced keloid-derived fibroblasts death, but Z-VAK-FMK (apoptotic inhibitor) did not. Interestingly, 5-ALA-PDT promoted the SIRT3 protein expression and the activity of mitochondrial superoxide dismutase 2 (SOD2), but SIRT1 protein expression level was decreased. SOD2 as a key enzyme can decrease mitochondrial ROS (mROS) level, Deacetylation of SOD2 by SIRT3 regulates SOD2 enzymatic activity has been identified. Then we explored SOD2 acetylation level with immunoprecipitation, found that 5-ALA-PDT significantly increased the acetylation levels of SOD2. In order to confirm deacetylation of SOD2 regulated by SIRT3, 3-TYP (SIRT3 inhibitor) was used. Found that inhibition of SIRT3 by 3-TYP significantly increased the level of SOD2 acetylation level compared with control group or 5-ALA-PDT group. To explore the connection of SIRT1 and SIRT3, cells were treated with EX527(SIRT1 inhibitor) or SRT1720 (SIRT1 activator), and EX527 increased SIRT3 protein level, however, SRT1720 displayed the opposite effect in the present or absence of 5-ALA-PDT. Moreover SIRT1-inhibited cells are more resistant to 5-ALA-PDT and showing decreased ROS accumulation. These results may demonstrate that 5-ALA-PDT induced SIRT1 protein level decreased, which promoted the effect of SIRT3 increased activity of SOD2 that can reduce mROS level, and then compromised 5-ALA-PDT induced autophagic cell death.
Ping Wang - One of the best experts on this subject based on the ideXlab platform.
-
SRT1720 a sirtuin 1 activator attenuates organ injury and inflammation in sepsis
Journal of Surgical Research, 2017Co-Authors: Adam Khader, Weng Lang Yang, Laura W Hansen, Salil R Rajayer, Jose M Prince, Jeffrey Nicastro, Gene F Coppa, Ping WangAbstract:Abstract 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. Materials and methods Male C57BL/6 mice (20-25 g) were subjected to cecal ligation and puncture (CLP) to induce sepsis. SRT1720 (5 or 20 mg/kg BW) or 10% dimethyl sulfoxide (vehicle) in 0.2-mL saline was injected intravenously at 5 h after CLP. Control animals were not subjected to any surgery. Blood and liver samples were harvested at 20 h after CLP for analysis. Results Administration of SRT1720 markedly reduced the serum levels of tissue injury markers (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) and renal injury markers (blood urea nitrogen and creatinine) in a dose-dependent manner after CLP. Furthermore, the levels of proinflammatory cytokines interleukin (IL)-1β and IL-6 in the serum and liver were significantly inhibited by SRT1720 treatment after CLP. SRT1720 treatment resulted in a significantly decreased mRNA expression of inflammasome components (nucleotide oligomerization domain–like receptor protein 3, adapter apoptosis-associated speck-like protein containing caspase-recruitment domain, IL-1β, and IL-18) in the liver, compared with the vehicle group. Conclusions SRT1720 treatment attenuates multiorgan injury in septic mice. SRT1720 treatment also decreases the production of proinflammatory cytokines and reduces inflammasome activation. Thus, pharmacologic stimulation of Sirt1 may present a promising therapeutic strategy for sepsis.
-
sirtuin 1 activator SRT1720 protects against organ injury induced by intestinal ischemia reperfusion
Shock, 2015Co-Authors: Laura W Hansen, Adam Khader, Weng Lang Yang, Jose M Prince, Jeffrey Nicastro, Gene F Coppa, Ping WangAbstract:Intestinal ischemia-reperfusion (I/R) occurs in various clinical situations and causes local and remote organ injury, especially in the lungs, leading to significant morbidity and mortality. The maintenance of mitochondrial biogenesis is essential for cell survival and is regulated in part by sirtuin 1 (SIRT1), an energy-sensing enzyme. We hypothesized that SIRT1 activation with SRT1720 would reduce local and remote organ injury after intestinal I/R. Intestinal I/R was induced by the occlusion of the superior mesenteric artery of adult male C57BL/6 mice for 45 min, followed by reperfusion for 4 h. SRT1720 or vehicle was injected intravenously at the time of reperfusion. Blood, small intestine, and lung tissues were collected for analysis. The SRT1720 treatment of I/R mice resulted in a 57% increase in protein levels of succinate dehydrogenase, an index of mitochondrial mass, and a 120% increase in messenger RNA levels of mitochondrial transcription factor A, a marker for mitochondrial biogenesis. The microscopic architecture and apoptosis of the gut tissue was improved in the SRT1720-treated I/R mice. SRT1720 decreased intestinal messenger RNA levels of tumor necrosis factor-α by 60% and inducible nitric oxide synthase to baseline after I/R. Systemic inflammation, as determined by serum interleukin-6, was reduced in treated mice. Lung injury, as measured by histological architecture and myeloperoxidase activity, and lung apoptosis were also improved after the SRT1720 treatment. SRT1720 preserved mitochondrial biogenesis and mass, leading to inhibition of inflammation and oxidative stress, thereby protecting against intestinal I/R-induced injury. Thus, the SIRT1-mediated pathway is a promising target for the treatment of intestinal I/R injury.
Tao Liu - One of the best experts on this subject based on the ideXlab platform.
-
Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway
Elsevier, 2019Co-Authors: Tao Liu, Tianxiang Ouyang, Huiping Chen, Yan Xiao, Yingying Huang, Jun LiuAbstract:Keloids exhibit cancer-like properties without spontaneous regression and usually recur post excision. Although photodynamic therapy (PDT) is a promising treatment, details of the mechanisms remain to be elucidated. In this study, we investigated mechanisms involved in 5-Aminolevulinic Acid (5-ALA)–based PDT against keloid. Found that 5-ALA-PDT induced superoxide anion-dependent autophagic cell death. Application of autophagy inhibitor 3-Methyladenine (3-MA) significantly prevented the effect that 5-ALA-PDT induced keloid–derived fibroblasts death, but Z-VAK-FMK (apoptotic inhibitor) did not. Interestingly, 5-ALA-PDT promoted the SIRT3 protein expression and the activity of mitochondrial superoxide dismutase 2 (SOD2), but SIRT1 protein expression level was decreased. SOD2 as a key enzyme can decrease mitochondrial ROS (mROS) level, Deacetylation of SOD2 by SIRT3 regulates SOD2 enzymatic activity has been identified. Then we explored SOD2 acetylation level with immunoprecipitation, found that 5-ALA-PDT significantly increased the acetylation levels of SOD2. In order to confirm deacetylation of SOD2 regulated by SIRT3, 3-TYP (SIRT3 inhibitor) was used. Found that inhibition of SIRT3 by 3-TYP significantly increased the level of SOD2 acetylation level compared with control group or 5-ALA-PDT group. To explore the connection of SIRT1 and SIRT3, cells were treated with EX527(SIRT1 inhibitor) or SRT1720 (SIRT1 activator), and EX527 increased SIRT3 protein level, however, SRT1720 displayed the opposite effect in the present or absence of 5-ALA-PDT. Moreover SIRT1-inhibited cells are more resistant to 5-ALA-PDT and showing decreased ROS accumulation. These results may demonstrate that 5-ALA-PDT induced SIRT1 protein level decreased, which promoted the effect of SIRT3 increased activity of SOD2 that can reduce mROS level, and then compromised 5-ALA-PDT induced autophagic cell death. Keywords: Keloid, 5-aminolevulinic acid, SIRT1, SIRT3, Autophag
-
efficacy of 5 aminolevulinic acid based photodynamic therapy against keloid compromised by downregulation of sirt1 sirt3 sod2 mros dependent autophagy pathway
Redox biology, 2019Co-Authors: Tao Liu, Tianxiang Ouyang, Huiping Chen, Yan Xiao, Yingying Huang, Jun LiuAbstract:Keloids exhibit cancer-like properties without spontaneous regression and usually recur post excision. Although photodynamic therapy (PDT) is a promising treatment, details of the mechanisms remain to be elucidated. In this study, we investigated mechanisms involved in 5-Aminolevulinic Acid (5-ALA)-based PDT against keloid. Found that 5-ALA-PDT induced superoxide anion-dependent autophagic cell death. Application of autophagy inhibitor 3-Methyladenine (3-MA) significantly prevented the effect that 5-ALA-PDT induced keloid-derived fibroblasts death, but Z-VAK-FMK (apoptotic inhibitor) did not. Interestingly, 5-ALA-PDT promoted the SIRT3 protein expression and the activity of mitochondrial superoxide dismutase 2 (SOD2), but SIRT1 protein expression level was decreased. SOD2 as a key enzyme can decrease mitochondrial ROS (mROS) level, Deacetylation of SOD2 by SIRT3 regulates SOD2 enzymatic activity has been identified. Then we explored SOD2 acetylation level with immunoprecipitation, found that 5-ALA-PDT significantly increased the acetylation levels of SOD2. In order to confirm deacetylation of SOD2 regulated by SIRT3, 3-TYP (SIRT3 inhibitor) was used. Found that inhibition of SIRT3 by 3-TYP significantly increased the level of SOD2 acetylation level compared with control group or 5-ALA-PDT group. To explore the connection of SIRT1 and SIRT3, cells were treated with EX527(SIRT1 inhibitor) or SRT1720 (SIRT1 activator), and EX527 increased SIRT3 protein level, however, SRT1720 displayed the opposite effect in the present or absence of 5-ALA-PDT. Moreover SIRT1-inhibited cells are more resistant to 5-ALA-PDT and showing decreased ROS accumulation. These results may demonstrate that 5-ALA-PDT induced SIRT1 protein level decreased, which promoted the effect of SIRT3 increased activity of SOD2 that can reduce mROS level, and then compromised 5-ALA-PDT induced autophagic cell death.
Anthony J Donato - One of the best experts on this subject based on the ideXlab platform.
-
the sirt1 activator SRT1720 reverses vascular endothelial dysfunction excessive superoxide production and inflammation with aging in mice
American Journal of Physiology-heart and Circulatory Physiology, 2014Co-Authors: Lindsey B Gano, Anthony J Donato, Hamza M Pasha, Christopher M Hearon, Amy L Sindler, Douglas R SealsAbstract:Reductions in arterial SIRT1 expression and activity with aging are linked to vascular endothelial dysfunction. We tested the hypothesis that the specific SIRT1 activator SRT1720 improves endotheli...
-
abstract 10813 chronic treatment with sirt1 activator SRT1720 ameliorates age associated vascular endothelial dysfunction in b6d2f1 mice
Circulation, 2010Co-Authors: Lindsey B Gano, Douglas R Seals, Muhammad Hamza, Lisa A Lesniewski, Anthony J DonatoAbstract:Background: Vascular endothelial dysfunction develops with aging, reflected by impaired endothelium-dependent dilation (EDD) mediated by oxidative stress and decreases in nitric oxide (NO) bioavail...
Melissa Mitchell - One of the best experts on this subject based on the ideXlab platform.
-
sirtuin 1 activation attenuates cardiac fibrosis in a rodent pressure overload model by modifying smad2 3 transactivation
Cardiovascular Research, 2018Co-Authors: Robert A Civitarese, Jean-francois Desjardins, Yanling Zhang, Antoinette Bugyeitwum, Christopher Ford, Jessica Seegobin, Suzanne L Advani, Golam Kabir, Melissa MitchellAbstract:Aims Transforming growth factor β1 (TGF-β1) is a prosclerotic cytokine involved in cardiac remodelling leading to heart failure (HF). Acetylation/de-acetylation of specific lysine residues in Smad2/3 has been shown to regulate TGF-β signalling 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. Herein, 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 signalling and the fibrotic response. Methods and results Eight weeks old male C57BL/6 mice were randomized to undergo sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Post-surgery, animals were further randomized to receive SRT1720 or vehicle treatment. Echocardiography, pressure-volume loops, and histological analysis revealed an impairment in cardiac function and deleterious left ventricular remodelling in TAC-operated animals that was improved with SRT1720 treatment. Genetic ablation and cell culture studies using a Smad-binding response element revealed SIRT1 to be a specific target of SRT1720 and identified Smad2/3 as a SIRT1 specific substrate. Conclusion Overall, our data demonstrate that Smad2/3 is a specific SIRT1 target and suggests that pharmacological activation of SIRT1 may be a novel therapeutic strategy to prevent/reverse HF via modifying Smad activity.
-
Abstract 19029: The Sirt1 Activator, SRT1720, Attenuates Cardiac Hypertrophy and Fibrosis in a Rodent Pressure Overload Model
Circulation, 2014Co-Authors: Christopher M Ford, Robert A Civitarese, Antoinette Bugyei-twum, Jean-francois Desjardins, Armin Abadeh, Jennifer Switzer, Melissa Mitchell, Kerri Thai, Yanling Zhang, Andrew AdvaniAbstract:Background: Transforming growth factor β1 ( TGFβ1) is a prosclerotic cytokine involved in cardiac remodeling leading to heart failure (CHF). In order to precisely regulate TGFβ1 signaling, acetylation/de-acetylation of lysine 19 within the MH1 domain of Smad2 has been shown to alter DNA binding and transcriptional activity. Recently the lysine de-acetylase Sirt1 has been shown to have a cardioprotective effect, however both Sirt1 expression and activity are reduced in CHF. We hypothesized that pharmacological activation of Sirt1 using SRT1720 would induce cardioprotection in a transverse aortic constriction (TAC) model through modulation of TGF-s/Smad signaling. Methods: Wildtype C57BL/6 mice were randomized to receive TAC or sham surgery at 8 weeks of age; each group was subsequently randomized to receive SRT1720 (100mg/kg/day) or placebo, administered once daily via oral gavage. Six weeks following TAC, cardiac function was assessed followed by left ventricular (LV) tissue collection for analysis. Results: Animals randomized to TAC demonstrated reduced systolic function, LV hypertrophy and increased fibrosis (all p Conclusion: Treatment of mice with SRT1720 improves cardiac function and reduces cardiac fibrosis and hypertrophy following TAC. Given that Sirt1 expression and activity are reduced in CHF, enhancing Sirt1 activity may represent a novel intervention to reduce TGF-s mediated fibrosis.