Journal: Cells

Article Title: Identification of PARP-1, Histone H1 and SIRT-1 as New Regulators of Breast Cancer-Related Aromatase Promoter I.3/II

doi: 10.3390/cells9020427

Figure Lengend Snippet: PARP-1 functionally interacts with histone deacetylases (HDACs). If not indicated otherwise, cells were stimulated with forskolin. ( A ) pGL3-PII-522 wt-transfected 3T3-L1 cells were incubated with n-butyrate, without or with PJ34 ( n = 6; * p < 0.05 versus n-butyrate only; # p < 0.05 versus controls). ( B ) 3T3-L1 cells transfected with pGL3-PII-522 wt or pGL3-PII-522(T-241C) were incubated with panobinostat ( n = 8; * p < 0.05 versus no panobinostat; # p < 0.05 wt versus T-241C), or ( C ) with selisistat alone or in combination with PJ34 ( n = 8; * p < 0.05 versus no PJ34; # p < 0.05 wt versus T-241C). ( D , E ) Aromatase mRNA-expression or activity was measured in BAFs, which were treated with selisistat without or with PARP-1 inhibitor PJ34. For better comparison, the data from BAFs not treated with selisistat (control) were taken from E–H (control). SIRT-1 inhibition alone reduced aromatase expression and activity. ( D ) Control n = 3, selisistat n = 6; # p < 0.05 control versus selisistat; ( E ) n = 3; * p < 0.05 versus no selisistat; # p < 0.05 control versus selisistat). ( F ) The increased NAD + /NADH ratios were measured in forskolin-stimulated BAFs with the inhibition of PARP-1 (5 µM PJ34) or/and SIRT-1 (200 nM selisistat) ( n = 3; * p < 0.05 versus forskolin alone).

Article Snippet: Furthermore, the cells were treated with PARP-1 inhibitor PJ34 (Selleck Chemicals S7300, Houston, TX, USA), HDAC class I/IIa inhibitor n-butyrate (Sigma B5887, Taufkirchen, Germany), HDAC class I/II/IV inhibitor Panobinostat (LBH589, Selleck Chemicals S1030) and SIRT-1 inhibitor selisistat (EX527, Selleck Chemicals S1541).

Techniques: Transfection, Incubation, Expressing, Activity Assay, Comparison, Control, Inhibition

Journal: Cell Reports

Article Title: SIN3A histone deacetylase action counteracts MUS81 to promote stalled fork stability

doi: 10.1016/j.celrep.2024.113778

Figure Lengend Snippet: Sin3A prevents fork breakage in stressed conditions (A) Images of cells immunostained for chr-bound RAD51 (green) and FANCD2 (red) proteins. DNA stained with DAPI (blue). Scale bar, 10 μm. siRNAs and HU as indicated. Plots show number of FANCD2 (left) or RAD51 (right) foci per cell. Mean in black. Data are pooled from 3 different assays. >1,500 cells scored per condition. ∗∗∗ p < 0.0001; two-tailed Mann-Whitney test. Immunoblot detection of Sin3A. H3, loading control. (B) Images of cells immunostained for γH2AX (red) and chr-bound RPA (green) proteins. DNA stained with DAPI (blue). Scale bar, 25 μm. Treatment as in (A). Histograms show the percentage (mean + SD) of γH2AX (top), chr-bound RPA-positive cells (left), and double-positive cells. n = 3. >400 cells scored per condition and assay. Negative staining determined in untreated control cells. ∗ p = 0.0346 (top) and p = 0.0231 (bottom left); ∗∗ p = 0.0037; unpaired two-tailed Student’s t test. (C) Images of U2OS SEC-C (cells stably expressing Cas9) cells immunostained for γH2AX (red) protein. DNA stained with DAPI (blue). Scale bar, 10 μm. RNA guides (72 h) and HU (3 mM, 4 h) as indicated. Immunoblot detection of Sin3A in indicated samples. GAPDH, loading control. Plot shows distribution of γH2AX intensity values. Median in black. Data are pooled from 2 different assays. >140 cells scored per condition. ∗∗∗ p < 0.0001; two-tailed Mann-Whitney test. (D) Plot shows distribution of γH2AX intensity values in cells treated (4 h) with HU (3 mM) combined with sodium butyrate (NaB, 5 mM), trichostatin A (TSA, 250 nM), and romidepsin (50 nM). Median in black. Data are pooled from 4, 2, and 3 different assays, respectively. >1,100 cells scored per condition. ∗∗∗ p < 0.0001; two-tailed Mann-Whitney test. (E) Images of cells immunostained for chr-bound 53BP1 (green) protein. DNA was stained with DAPI (blue). Scale bar, 10 μm. siRNAs and HU as indicated. Plot shows number of 53BP1 foci per cell. Data are pooled from 3 different assays. >1,400 cells were scored per condition. ∗∗∗ p < 0.0001; two-tailed Mann-Whitney test. (F) Representative images of comet assay. Scale bar, 100 μm. siRNAs and HU as indicated. Histogram shows tail moment (mean + SD). n = 3. ∗∗ p = 0.0067; two-tailed unpaired Student’s t test. (G) Same as in (F) in indicated samples. Scale bar, 100 μm. Histogram shows tail moment (mean + SD). n = 4. n.s. p = 0.1087; two-tailed unpaired Student’s t test. Immunoblot detection of MTA2. GAPDH, loading control. siMTA2, MTA2 siRNA-transfected cells. HU (3 mM, 24 h) except for (C) and (D). siRNA transfection (72 h). All replicates are biological replicates. See also Figure S2 .

Article Snippet: Romidepsin (Class I HDACi) , Selleckchem , FR228.

Techniques: Staining, Two Tailed Test, MANN-WHITNEY, Western Blot, Control, Negative Staining, Stable Transfection, Expressing, Single Cell Gel Electrophoresis, Transfection

Journal: Cell Reports

Article Title: SIN3A histone deacetylase action counteracts MUS81 to promote stalled fork stability

doi: 10.1016/j.celrep.2024.113778

Figure Lengend Snippet:

Article Snippet: Romidepsin (Class I HDACi) , Selleckchem , FR228.

Techniques: Recombinant, Control, Protease Inhibitor, Imaging, Reverse Transcription, Plasmid Preparation, Software, Magnetic Beads, Blocking Assay, In Situ, Western Blot, Membrane

Journal: Neuropharmacology

Article Title: Differential effects of HDAC inhibitors on PPN oscillatory activity in vivo

doi: 10.1016/j.neuropharm.2019.107922

Figure Lengend Snippet: A. Ramp-induced oscillations in the presence of SB+TTX (3 μM) and 15 min after SB+TTX (10 μM). B. Power spectrum corresponding to the same cell shown in A. C. Bar graph representing mean oscillation frequency for all PPN neurons recorded from Vehicle (black bar; n=19 cells), MS275 low dose (dashed blue bar; 4 mg/Kg, i.p.; n=12 cells), and MS275 middle dose (solid blue bar; 20 mg/Kg, i.p.; n=16 cells) treatments. No significant differences were observed (One Way ANOVA, F(2,46)=1.1, p=0.3). D. Bar graph representing mean oscillation amplitude for PPN neurons from Vehicle (black bar; n=17 cells), MS275 middle dose (dashed blue bar; 20 mg/Kg, i.p.; n= 10 cells), and MS275 high dose (solid blue bar; 100 mg/Kg, i.p.; n=17 cells) treatments. Significantly higher oscillation amplitudes were observed for TSA high dose (100 mg/Kg) treatment. One-way ANOVA, F(2,43)=4.4, p=0.02. * P<0.05, post hoc Tukey’s test, MS275 (100 mg/Kg) vs Vehicle, q=3.9, p=0.02. E. Bar graph representing mean input resistance (Rm) for PPN neurons from Vehicle (black bar; n=19 cells), MS175 low dose (dashed blue bar; 4 mg/Kg, i.p.; n=12 cells), and MS275 middle dose (solid blue bar; 20 mg/Kg, i.p.; n=16 cells) treatments. No significant differences were observed (One Way ANOVA F(2,46)=0.008, p=0.9).

Article Snippet: HDACi in vivo administration (acute, single dose) was performed with the following agents: the selective HDAC class IIa inhibitor, MC1568 (4 or 20 mg/Kg, i.p. ; Catalog #M1824; Sigma Aldrich, St. Louis, MO, USA or Catalog #4077; TOCRIS, MN, USA) [3-[5-(3-(3-Fluorophenyl)-3-oxopropen-1-yl)-1-methyl-1H-pyrrol-2-yl]-N-hydroxy-2-propenamide]; the HDAC class I & II inhibitor Trichostatin-A (4 or 20 mg/Kg, i.p. ; Catalog #T8552; Sigma Aldrich, St. Louis, MO, USA or Catalog #1406; TOCRIS, MN, USA) [(2E,4E,6R)-7-(4-(Dimethylamino)phenyl)-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide]; and a HDAC class I inhibitor MS275 (20 or 100 mg/Kg, i.p. ; Catalog #EPS002; Sigma Aldrich, St. Louis, MO, USA or Catalog #6208; TOCRIS, MN, USA) [Pyridin-3-yl)methyl 4-(2-aminophenylcarbamoyl) benzylcarbamate].

Techniques:

Journal: Neuropharmacology

Article Title: Differential effects of HDAC inhibitors on PPN oscillatory activity in vivo

doi: 10.1016/j.neuropharm.2019.107922

Figure Lengend Snippet: A. Representative ICa (current density values, pA/pF) recordings in PPN neurons elicited by a 50 msec long depolarizing square step from a holding potential of −50 mV to 0 mV after Vehicle (black record), MC1568 (red record), TSA (brown record), and MS275 (blue record) treatments. B. Percent change of ICa amplitude after Vehicle (black bar; n=39 cells), 20 mg/Kg MC1568 (red bar; n=17 cells), 20 mg/Kg TSA (brown bar; n=12 cells), and 20 mg/Kg MS275 treatments (blue bar; n=11 cells). One Way ANOVA, F(3,77)=24.3, p<0.001. * p<0.05; ICa comparing all treatments; post hoc Tukey’s test, 20mg/Kg MC1568 vs Vehicle, q=8.1, p<0.001; 20 mg/Kg TSA vs Vehicle, q=6.8, p<0.001; 20 mg/Kg MS275 vs Vehicle, q=4.3, p=0.016. # P<0.05 post hoc Tukey’s test, 20 mg/Kg MS275 vs 20 mg/Kg MC1568, q=9.9, p<0.001; 20 mg/Kg MS275 vs 20 mg/Kg TSA, q=8.9, p<0.001. C. Percent change of ICa amplitude after Vehicle (black bar; n=16 cells), 4 mg/Kg MC1568 (red bar; n=9 cells), 4 mg/Kg TSA (brown bar; n=11 cells), and 100 mg/Kg MS275 treatments (blue bar; n=15 cells). One Way ANOVA, F(3,50)=8.0, p<0.001. * p<0.05; ICa comparing all treatments; post hoc Tukey’s test, 100 mg/Kg MS275 vs Vehicle, q=4.3, p<0.01; MC1568 4 mg/Kg vs Vehicle, q=4.1, p=0.03. No statistically significant differences were observed comparing 4 mg/Kg TSA vs Vehicle, q=1.4, p=0.7. # p<0.05 post hoc Tukey’s test, 100 mg/Kg MS275 vs 4 mg/Kg MC1568, q=6.8, p<0.001; 4 mg/Kg TSA vs 4 mg/Kg MC1568, q=5.0, P=0.005; 100 mg/Kg MS275 vs Vehicle, q=4.3, p<0.005. No statistically significant differences were observed comparing 20mg/Kg vs 100 mg/Kg MS275, one way ANOVA, F(1,25)=0.02, p=0.9.

Article Snippet: HDACi in vivo administration (acute, single dose) was performed with the following agents: the selective HDAC class IIa inhibitor, MC1568 (4 or 20 mg/Kg, i.p. ; Catalog #M1824; Sigma Aldrich, St. Louis, MO, USA or Catalog #4077; TOCRIS, MN, USA) [3-[5-(3-(3-Fluorophenyl)-3-oxopropen-1-yl)-1-methyl-1H-pyrrol-2-yl]-N-hydroxy-2-propenamide]; the HDAC class I & II inhibitor Trichostatin-A (4 or 20 mg/Kg, i.p. ; Catalog #T8552; Sigma Aldrich, St. Louis, MO, USA or Catalog #1406; TOCRIS, MN, USA) [(2E,4E,6R)-7-(4-(Dimethylamino)phenyl)-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide]; and a HDAC class I inhibitor MS275 (20 or 100 mg/Kg, i.p. ; Catalog #EPS002; Sigma Aldrich, St. Louis, MO, USA or Catalog #6208; TOCRIS, MN, USA) [Pyridin-3-yl)methyl 4-(2-aminophenylcarbamoyl) benzylcarbamate].

Techniques:

Journal: Neuropharmacology

Article Title: Differential effects of HDAC inhibitors on PPN oscillatory activity in vivo

doi: 10.1016/j.neuropharm.2019.107922

Figure Lengend Snippet: A. Representative ramp-induced oscillations of PPN neurons from a rat treated systemically with MS275 (100 mg/Kg, i.p.; left panel) or MS275+MC1568 (100 mg/Kg+20 mg/Kg; right panel) in the presence of SB+TTX. B. Bar graph representing mean amplitude of oscillations in PPN neurons from a MS275 (black bar; 100 mg/Kg; n=17 cells) or a MS275+MC1568 (100 mg/Kg+20 mg/Kg; grey bar; n=6 cells) treated rat. Significantly lower amplitudes were observed for the combination MS275+MC1568 treatment. * P<0.05, One-way ANOVA, F(1,22)=7.3, p=0.01, post hoc Tukey’s test, MS275+MC1568 vs MS275, q=3.8, p=0.01. C. Bar graph representing mean frequency of oscillations for PPN neurons from a MS275 (black bar; 100 mg/Kg; n=16 cells) or a MS275+MC1568 (100 mg/Kg+20 mg/Kg; grey bar; n=6 cells) treated rat. No significant differences were observed (One Way ANOVA, F(2,21)=0.2, p=0.7). D. Bar graph representing mean input resistance (Rm) for PPN neurons from a MS275 (black bar; 100 mg/Kg; n=16 cells) or a MS275+MC1568 (100 mg/Kg+20 mg/Kg; grey bar; n=6 cells) treated rat. No significant differences were observed (One Way ANOVA, F(2,21)=1.0, p=0.3).

Article Snippet: HDACi in vivo administration (acute, single dose) was performed with the following agents: the selective HDAC class IIa inhibitor, MC1568 (4 or 20 mg/Kg, i.p. ; Catalog #M1824; Sigma Aldrich, St. Louis, MO, USA or Catalog #4077; TOCRIS, MN, USA) [3-[5-(3-(3-Fluorophenyl)-3-oxopropen-1-yl)-1-methyl-1H-pyrrol-2-yl]-N-hydroxy-2-propenamide]; the HDAC class I & II inhibitor Trichostatin-A (4 or 20 mg/Kg, i.p. ; Catalog #T8552; Sigma Aldrich, St. Louis, MO, USA or Catalog #1406; TOCRIS, MN, USA) [(2E,4E,6R)-7-(4-(Dimethylamino)phenyl)-N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadienamide]; and a HDAC class I inhibitor MS275 (20 or 100 mg/Kg, i.p. ; Catalog #EPS002; Sigma Aldrich, St. Louis, MO, USA or Catalog #6208; TOCRIS, MN, USA) [Pyridin-3-yl)methyl 4-(2-aminophenylcarbamoyl) benzylcarbamate].

Techniques:

Journal: Cell Death Discovery

Article Title: Acetylation of Checkpoint suppressor 1 enhances its stability and promotes the progression of triple-negative breast cancer

doi: 10.1038/s41420-022-01269-x

Figure Lengend Snippet: A Endogenous IP assay showed the acetylated CHES1 in the presence of pan-HDACs inhibitors. B CoIP assay showed that CHES1 could be acetylated by p300 but not other acetyltransferases. “*” denotes the non-specific band. C CoIP assay showed the disability of catalytic deficient mutants of p300 on the acetylation of CHES1. D , E CoIP assay showed the endogenous interaction between CHES1 and p300 in TNBC. F IP assay showed the effect of HDACs inhibitors on the acetylation levels of CHES1. G The schematic diagram of the main steps for identifying the acetylation lysine sites of CHES1 by mass spectrometry (MS). H Tandem mass spectrum of the peptide (m/z = 491.59) HNLSLNKCFKK containing acetylated K170 and K173 of CHES1. The “ac” above the Lys indicates an acetyl remnant on this Lys. I The schematic representation of the 21 acetylated lysine sites in the protein domains of CHES1. J CoIP assay showed the acetylation levels of wild type CHES1 and its KR mutant.

Article Snippet: Class I HDACs inhibitor Trichostatin A (TSA) (S1045), specific inhibitor for HDAC1 (Entinostat/MS-275, S1053), HDAC2 (CAY10683, S7595), p300 (C646, S7152), p300/CBP (SGC-CBP30, S7256), Puromycin (S7417), and proteasome inhibitor (MG132, S2619) were purchased from Selleck (USA).

Techniques: Co-Immunoprecipitation Assay, Mass Spectrometry, Mutagenesis

Journal: Cell Death Discovery

Article Title: Acetylation of Checkpoint suppressor 1 enhances its stability and promotes the progression of triple-negative breast cancer

doi: 10.1038/s41420-022-01269-x

Figure Lengend Snippet: A The effect of HDACs inhibitors on the protein levels of exogenous CHES1. B Western blot showed the half-life of wild type CHES1 and its KR mutant after treating with 10 μg/ml CHX. The line graph showed the relative intensity of CHES1 protein levels in different time normalized by β-actin, *** p ＜0.001. C IP assay showed the polyubiquitination levels of wild type CHES1 and its KR mutant with or without treatment of 20 μg/ml MG132 for 6 h. D IP assay detected the acetylation and ubiquitination of endogenous CHES1 in different types of breast cancer cells pretreated with TSA and NAM. “*” denotes the non-specific band. E CoIP assay showed the endogenous interaction between CHES1 and HDAC1 in MCF7 and MDA-MB-231 cells.

Article Snippet: Class I HDACs inhibitor Trichostatin A (TSA) (S1045), specific inhibitor for HDAC1 (Entinostat/MS-275, S1053), HDAC2 (CAY10683, S7595), p300 (C646, S7152), p300/CBP (SGC-CBP30, S7256), Puromycin (S7417), and proteasome inhibitor (MG132, S2619) were purchased from Selleck (USA).

Techniques: Western Blot, Mutagenesis, Ubiquitin Proteomics, Co-Immunoprecipitation Assay

Journal: Molecular Neurobiology

Article Title: HDAC7 Activates IKK/NF-κB Signaling to Regulate Astrocyte-Mediated Inflammation

doi: 10.1007/s12035-022-02965-6

Figure Lengend Snippet: Pharmacological inhibition of HDAC7 with TMP195 suppresses LPS-induced NF-κB activation and inflammatory responses in primary cultured astrocytes. A – C TMP195 blocks LPS-induced NF-κB phosphorylation in cultured astrocytes. A Representative western blots showing protein levels of p-NF-κB(S468), p-NF-κB(S536), NF-κB, and β-actin in LPS- and TMP195-treated primary cultured mouse astrocytes (astrocytes were incubated with LPS (100 ng/ml), LPS (100 ng/ml) + TMP195 (3 μM), LPS (100 ng/ml) + TMP195 (5 μM), or control vehicle for 24 h). B Quantification of p-NF-κB(S468) normalized to total NF-κB. C Quantification of p-NF-κB(S536) normalized to total NF-κB. N = 6 for each group, one-way ANOVA, Dunnett’s post hoc analysis. D Representative confocal images showing decreased nuclear NF-κB expression by TMP195 in LPS-stimulated astrocytes described as above. Scale bar, 10 μm. E Quantification of nuclear/cytoplasm NF-κB fluorescence ratio. N = 21–37 cells from 6 independent dishes for each group, one-way ANOVA, Dunnett’s post hoc analysis. F – J TMP195 reverses LPS-induced inflammatory responses in cultured astrocytes. F RT-qPCR analysis of Il-1α, Il-1β, Il6, Tnfα, iNOS, and COX-2 in LPS and TMP195- treated astrocytes described as above astrocytes described as above. G Representative western blots showing protein levels of GFAP, iNOS, COX-2, Il-1α, and β-actin in primary astrocytes treated as described above. Quantification of iNOS ( H ), COX-2 ( I ), and Il-1α ( J ) normalized to β-actin. N = 6 for each group, one-way ANOVA, Dunnett’s post hoc analysis. Data were expressed as mean ± SEM, **p < 0.01, ***p < 0.001

Article Snippet: TMP195 (a selective class IIa HDAC inhibitor) was purchased from Selleck (Shanghai, China).

Techniques: Inhibition, Activation Assay, Cell Culture, Phospho-proteomics, Western Blot, Incubation, Control, Expressing, Fluorescence, Quantitative RT-PCR

Journal: Molecular Neurobiology

Article Title: HDAC7 Activates IKK/NF-κB Signaling to Regulate Astrocyte-Mediated Inflammation

doi: 10.1007/s12035-022-02965-6

Figure Lengend Snippet: TMP195 decreases LPS-induced NF-κB activation and inflammation in vivo. A Schematic diagram of the experimental procedure in mice. 2-month-old wildtype C57BL/6 male mice were pre-injected with TMP195 (30/50 mg/kg) or vehicle 2 h before LPS (3 mg/kg) injection and received another injection of TMP195 (30/50 mg/kg) 6 h after LPS treatment. B – I TMP195 attenuates LPS-induced NF-κB activation in vivo. B Representative western blots showing protein levels of GFAP, p-NF-κB(S468), p-NF-κB(S536), NF-κB, and β-actin in hippocampus. C – E Quantification of p-NF-κB(S468) normalized to total NF-κB ( C ), p-NF-κB(S536) normalized to total NF-κB ( D ), and GFAP normalized to β-actin ( E ) in hippocampus. F Representative western blots showing protein levels of GFAP, p-NF-κB(S468), p-NF-κB(S536), NF-κB, and β-actin in cortex. G – I Quantification of p-NF-κB(S468) normalized to total NF-κB ( G ), p-NF-κB(S536) normalized to total NF-κB ( H ), and GFAP normalized to β-actin ( I ) in cortex. N = 6 for each group, one-way ANOVA, Dunnett’s post hoc analysis. J and K TMP195 reverses LPS-induced inflammatory gene expression in vivo. J RT-qPCR analysis of Il-1α, Il-1β, Tnfα, Gfap, C3, and Lcn2 gene expression in hippocampus. K RT-qPCR analysis of Il-1α, Il-1β, Tnfα, Gfap, C3, and Lcn2 gene expression in cortex. N = 6 for each group, one-way ANOVA, Dunnett’s post hoc analysis. Data were expressed as mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001

Article Snippet: TMP195 (a selective class IIa HDAC inhibitor) was purchased from Selleck (Shanghai, China).

Techniques: Activation Assay, In Vivo, Injection, Western Blot, Gene Expression, Quantitative RT-PCR

Journal: Molecular Neurobiology

Article Title: HDAC7 Activates IKK/NF-κB Signaling to Regulate Astrocyte-Mediated Inflammation

doi: 10.1007/s12035-022-02965-6

Figure Lengend Snippet: TMP195 reverses LPS-induced gliosis and anxiety-like behaviors in vivo. A – C TMP195 limits LPS-induced gliosis. A Representative confocal image of GFAP and Iba1 in the hippocampal CA1 subset. Scale bar, 40 μm. B Quantification of GFAP and C Iba1 immunofluorescence intensity in the hippocampus. N = 4–5 for each group, one-way ANOVA, Dunnett’s post hoc analysis. D and E TMP195 attenuates LPS-induced nuclear NF-κB activation in the astrocytes. D Representative hippocampal confocal images showing decreased nuclear NF-κB expression by TMP195 in LPS-injected mice. Scale bar, 40 μm. E Quantification of nuclear NF-κB fluorescence coverage in GFAP positive cells. N = 38–54 cells from 4–5 mice for each group, one-way ANOVA, Dunnett’s post hoc analysis. F – I TMP195 attenuates LPS-induced anxiety-like behaviors in the open field test. In this test, the exploring performance in the center region (green frame area) is tested. F Representative moving traces of mice during the open field test. TMP195 treatment attenuates LPS-induced exploring disorders represented by increased center moving distance ( G ) and center exploring time ( H ) in the open field test. I The total moving distances are comparable in all four groups. N = 9–14 mice, one-way ANOVA, Dunnett’s post hoc analysis. J – M TMP195 ameliorates LPS-induced anxiety-like behaviors in the elevated plus maze. J Representative moving traces of mice during the elevated plus maze. TMP195 treatment improved exploring capacity of LPS-injected mice shown by increased open arm travel distance ( K ), open arm exploring time ( L ), and open arm entries ( M ) in the elevated plus maze. N = 9–12 mice, one-way ANOVA, Dunnett’s post hoc analysis. Data were expressed as mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001

Article Snippet: TMP195 (a selective class IIa HDAC inhibitor) was purchased from Selleck (Shanghai, China).

Techniques: In Vivo, Immunofluorescence, Activation Assay, Expressing, Injection, Fluorescence

Journal: Oxidative Medicine and Cellular Longevity

Article Title: HDAC4 Inhibitors as Antivascular Senescence Therapeutics

doi: 10.1155/2022/3087916

Figure Lengend Snippet: HDAC4 inhibitors in the research and development pipelines.

Article Snippet: Two other HDAC4 inhibitors, mocetinostat dihydrobromide and a class IIa HDAC inhibitor, both developed by MethylGene Inc., are undergoing extensive clinical trials for the treatment of multiple cancers including advanced solid tumor and metastatic non-small-cell lung cancer.

Techniques:

Journal: Oxidative Medicine and Cellular Longevity

Article Title: HDAC4 Inhibitors as Antivascular Senescence Therapeutics

doi: 10.1155/2022/3087916

Figure Lengend Snippet: The structures of HDAC are divided into groups A, B, C, and D for the attachment or binding of histone deacetylases (HDACs). Group A inhibitors are soft, with nonbonding electron-pair donors that coordinate the zinc ion and H-bond acceptor to accept a hydrogen bond from tyrosine –OH. An H-bond could be donated to the phenol oxygen atom of Tyr297. Group B links the zinc-chelating moiety to the spacer and hence is at least trivalent. Group C includes H-bond donors to residue His132; consequently, they are trivalent or of higher valency. Group D includes proton donors that protonate His131, subsequently accepting an ionic H-bond from it and forming a strong interaction with the zinc ion.

Article Snippet: Two other HDAC4 inhibitors, mocetinostat dihydrobromide and a class IIa HDAC inhibitor, both developed by MethylGene Inc., are undergoing extensive clinical trials for the treatment of multiple cancers including advanced solid tumor and metastatic non-small-cell lung cancer.

Techniques: Binding Assay, Residue