Journal: International journal of molecular sciences

Article Title: Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease.

doi: 10.3390/ijms24086968

Figure Lengend Snippet: Figure 5. Alteration of the relative density of intracellular metabolic controllers in synapses (A– C) and outside synapses (D–F) in the cerebral cortex of 9-month-old female WT and APP/PS1 mice. (A–C) Cerebrocortical synaptosomes (purified synapses) from APP/PS1 mice displayed a decreased density of sirtuin 1 (SIRT1; (A)), whereas there was no change in the density of sirtuin 3 (SIRT3; (B)) or of sestrin 2 (SESN2; (C)). (D–F) In total extracts (mostly extra-synaptic content) from APP/PS1 mice, there was a decreased density of SIRT1 (D) and of SESN2 (F), whereas there was no change in the density of SIRT3 (E). GAPDH (1:5000) was used as a loading control and results are presented as a ratio between the density of the protein of interest and GAPDH. Data are mean ± SEM of 4–7 experiments (number of different animals tested). ? p < 0.05 and ?? p < 0.01, using a Student’s unpaired t-test.

Article Snippet: The SIRT1 activator SRT2104 (4-methyl-N-[2-[3-(morpholin-4-ylmethyl)imidazo[2,1-b][1,3] thiazol-6-yl]phenyl]-2-pyridin-3-yl-1,3-thiazole-5-carboxamide) was purchased from MedChemExpress (Cat# HY-15262) and the SIRT1 inhibitor Ex-527 (6-chloro-2,3,4,9-tetrahydro-1Hcarbazole-1-carboxamide, Sigma, E7034) was obtained from Tocris (Cat# 2780).

Techniques: Control

Journal: International journal of molecular sciences

Article Title: Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease.

doi: 10.3390/ijms24086968

Figure Lengend Snippet: Figure 6. Effect of the pharmacological activation and inhibition of SIRT1 on PFC-LTP in 9-month- old WT and APP/PS1 mice. (A) Scheme of the experimental protocols illustrating the timing of addition of the different tested drugs in the electrophysiological experiments. (B) Time course and (C) summary graph showing that activation of SIRT1 with SRT2104 (10 µM) decreased the magnitude of LTP, while inhibition of SIRT1 with Ex-527 (1 µM) showed a tendency (p = 0.0896) to decrease the magnitude of LTP in the PFC of WT mice. There was no effect of SRT2104 on top of Ex-527. (D) Time course and (E) summary graph showing that activation of SIRT1 with SRT2104 did not affect LTP magnitude, while SIRT1 inhibition with Ex-527 significantly increased the magnitude of LTP in the PFC of APP/PS1 mice. Data are mean ± SEM of 3–12 experiments (number of different animals tested). ** p < 0.01, one-way ANOVA test.

Article Snippet: The SIRT1 activator SRT2104 (4-methyl-N-[2-[3-(morpholin-4-ylmethyl)imidazo[2,1-b][1,3] thiazol-6-yl]phenyl]-2-pyridin-3-yl-1,3-thiazole-5-carboxamide) was purchased from MedChemExpress (Cat# HY-15262) and the SIRT1 inhibitor Ex-527 (6-chloro-2,3,4,9-tetrahydro-1Hcarbazole-1-carboxamide, Sigma, E7034) was obtained from Tocris (Cat# 2780).

Techniques: Activation Assay, Inhibition

Journal: Oxidative Medicine and Cellular Longevity

Article Title: SIRT1 Modulators in Experimentally Induced Liver Injury

doi: 10.1155/2019/8765954

Figure Lengend Snippet: Effects of resveratrol and EX-527 pretreatment in lipopolysaccharide-induced acute hepatitis in D-galactosamine-sensitized rats (D-GalN/LPS) on the levels of (a) plasma ALT, (b) TBARS in homogenate and (c) SIRT1 expression. CO: control group; RES: 2.3 mg/kg resveratrol; D-GalN + LPS: 400 mg/kg D-galactosamine with 10 μ g/kg lipopolysaccharide; RES + D-GalN + LPS: 2.3 mg/kg resveratrol + D-GalN + LPS; EX − 527 + RES + D-GalN + LPS: 1 mg/kg EX-527 plus a combination of previous substances. Data are expressed as means ± SEM ( n = 6). a P < 0.05 versus CO. b P < 0.05 versus RES. c P < 0.05 versus D-GalN + LPS. d P < 0.05 versus RES + D-GalN + LPS (courtesy of Physiological Research , reference ).

Article Snippet: To address the ambiguity surrounding “resveratrol and similar polyphenols” and sirtuins, Sirtris Pharmaceuticals Inc. developed a number of synthetic SIRT1 activators: SRT1460, SRT1720, SRT2183, and SRT2104.

Techniques: Clinical Proteomics, Expressing, Control

Journal: Oxidative Medicine and Cellular Longevity

Article Title: SIRT1 Modulators in Experimentally Induced Liver Injury

doi: 10.1155/2019/8765954

Figure Lengend Snippet: Effects of quercetin and SRT1720 pretreatments on (a) SIRT1 and (b) HO-1 protein expressions in lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized (D-GalN/LPS) rats after 24 hours. Beta-actin was used as an endogenous control. CO: negative control, vehicle only; Q: quercetin 50 mg/kg; SRT1720: SRT1720 5 mg/kg; D-GalN/LPS: D-galactosamine 400 mg/kg + lipopolysaccharide 10 μ g/kg; Q + D-GalN/LPS: combination of Q and D-GalN/LPS; SRT1720 + D-GalN/LPS: combination of SRT1720 and D-GalN/LPS. ∗ indicates significant values ( P ≤ 0.05) compared to the negative control group (vehicle only); # indicates significant values ( P ≤ 0.05) compared to the D-GalN/LPS group. The results are expressed as means ± SEM, n = 5 (courtesy of Physiological Research , reference ).

Article Snippet: To address the ambiguity surrounding “resveratrol and similar polyphenols” and sirtuins, Sirtris Pharmaceuticals Inc. developed a number of synthetic SIRT1 activators: SRT1460, SRT1720, SRT2183, and SRT2104.

Techniques: Control, Negative Control

Journal: Oxidative Medicine and Cellular Longevity

Article Title: SIRT1 Modulators in Experimentally Induced Liver Injury

doi: 10.1155/2019/8765954

Figure Lengend Snippet: Effects of quercetin and carbon tetrachloride treatments on SIRT1 and heme oxygenase-1 (HO-1) expressions. (a) Representative Western blot image. (b) Quantification of SIRT1 expression by densitometry. (c) Quantification of HO-1 protein expression by densitometry. Beta-actin was used as an endogenous control. CO: negative control, vehicle only; Q: quercetin; CTC: carbon tetrachloride; Q + CTC: quercetin plus carbon tetrachloride. Data are presented as mean ± SEM, n = 6. ∗ P < 0.05, ∗∗ P < 0.01, or ∗∗∗ P < 0.001 relative to the CO group (vehicle only). ## P < 0.01 relative to the CTC group (courtesy of Elsevier , reference ).

Article Snippet: To address the ambiguity surrounding “resveratrol and similar polyphenols” and sirtuins, Sirtris Pharmaceuticals Inc. developed a number of synthetic SIRT1 activators: SRT1460, SRT1720, SRT2183, and SRT2104.

Techniques: Western Blot, Expressing, Control, Negative Control

Journal: Oxidative Medicine and Cellular Longevity

Article Title: SIRT1 Modulators in Experimentally Induced Liver Injury

doi: 10.1155/2019/8765954

Figure Lengend Snippet: Effects of sirtuin 1-activating compounds (STACs) and inhibitors on chemically induced hepatotoxicity. Hepatotoxins, like D-GalN/LPS and CTC, induce the formation of ROS/RNS in hepatocytes leading to oxidative stress, inflammation, and cell death. SIRT1 is activated and inhibited by stress-responsive factors and plays a dynamic role in regulating cytoprotection and apoptosis depending on the dosing schedule. SIRT1 activation by STACs results to a decrease of cell death and an increase in stress adaptation of hepatocytes due to the activation (↑) or the inhibition (↓) of various signaling and antioxidant molecules (not all included). These hepatoprotective effects can be blocked by administration of SIRT1 inhibitors. Blue →: activation; red ─●: inhibition; AMPK: AMP-activated protein kinase; CTC: carbon tetrachloride; D-GalN: D-galactosamine; FOXOs: forkhead homeobox type O family including FoxO1, FoxO3, and FoxO4; GADD45: growth arrest and DNA damage-inducible protein; GCL: glutamate cysteine ligase; GST: glutathione transferase; HO-1: heme oxygenase-1; IL-1/6: interleukin-1/6; iNOS: inducible nitric oxide synthase; JNK: c-Jun N-terminal kinase; LPS: lipopolysaccharide; miR-34a: microRNA-34a; NAD + : nicotinamide adenine dinucleotide; p53: tumor suppressor protein p53; PGC-1 α : peroxisome proliferator-activated receptor gamma coactivator 1 alpha; Prx: peroxiredoxins; RelA/p65/NF- κ B: RelA/p65 subunit of nuclear factor kappa-B; ROS: reactive oxygen species; RNS: reactive nitrogen species; SIRT1: silent information regulator (two) 1 (sirtuin 1); SOD2: superoxide dismutase 2; TNF- α : tumor necrosis factor-alpha.

Article Snippet: To address the ambiguity surrounding “resveratrol and similar polyphenols” and sirtuins, Sirtris Pharmaceuticals Inc. developed a number of synthetic SIRT1 activators: SRT1460, SRT1720, SRT2183, and SRT2104.

Techniques: Activation Assay, Inhibition