REGULATION OF HISTONE ACETYLATION IN THE HIPPOCAMPUS OF CHRONICALLY STRESSED RATS: A POTENTIAL ROLE OF SIRTUINS.

Slides:

Advertisements

Similar presentations

SIRT1 (Sirtuin 1) A mamalian NAD+-dependent hitone deacetylase (HDAC) It deacetylates tumor suppressor.

Advertisements

Materials and Methods Phase 1 Evaluated acute effects on fasting blood glucose and on post-oral glucose Groups 1 and 3 received distilled water Groups.

The effects of metabotropic glutamate receptors in NMDA receptor dependent long-term potentiation in hippocampus Zhou Su-ya.

Long-Term Voluntary Exercise and the Mouse Hypothalamic-Pituitary-Adrenocorticoid Axis: Impact of Concurrent Treatment with the Antidepressant Drug Tianeptine.

Date of download: 7/7/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Functional NPY Variation as a Factor in Stress Resilience.

From: Acetylation Preserves Retinal Ganglion Cell Structure and Function in a Chronic Model of Ocular Hypertension Invest. Ophthalmol. Vis. Sci ;55(11):

* Figure A in S1 File Body weight (g) n=8/group

The chemokine CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells Jungsook Cho, Donna L. Gruol Journal of.

Sirt1 modulates premature senescence-like phenotype in human endothelial cells Hidetaka Ota, Masahiro Akishita, Masato Eto, Katsuya Iijima, Masao Kaneki,

Visfatin Reduces Gap Junction Mediated Cell-to-Cell Communication in Proximal Tubule-Derived Epithelial Cells Cell Physiol Biochem 2013;32:

Fig. 1 Effect of l-T4 and E2 on MAPK activation and serine-118 phosphorylation of ERα in MCF-7 cells. A, MCF-7 cells were treated.

A B C D Supplementary Figure 1 CMV p300

Nuclear Factor of Activated T Cells 5 Deficiency Increases the Severity of Neuronal Cell Death in Ischemic Injury Neurosignals 2012;20:237–251 - DOI: /

Volume 36, Issue 1, Pages (September 2002)

Volume 85, Issue 3, Pages (March 2014)

Volume 51, Issue 1, Pages (July 2009)

Volume 81, Issue 1, Pages (January 2012)

Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway.

M. -H. Moon, J. -K. Jeong, Y. -J. Lee, J. -W. Seol, C. J. Jackson, S

Angiogenic effects of stromal cell-derived factor-1 (SDF-1/CXCL12) variants in vitro and the in vivo expressions of CXCL12 variants and CXCR4 in human.

Duodenal Reflux Leads to Down Regulation of DNA Mismatch Repair Pathway in an Animal Model of Esophageal Cancer Pramod Bonde, MD, MS, Daqing Gao, PhD,

Histone deacetylase inhibitors increase microRNA-146a expression and enhance negative regulation of interleukin-1β signaling in osteoarthritis fibroblast-like.

A Histone Deacetylase Inhibitor LBH589 Downregulates XIAP in Mesothelioma Cell Lines Which is Likely Responsible for Increased Apoptosis With TRAIL James.

Volume 44, Issue 2, Pages (February 2006)

Volume 134, Issue 2, Pages (July 2008)

Volume 16, Issue 10, Pages (September 2016)

Lori Redmond, Amir H. Kashani, Anirvan Ghosh Neuron

Volume 130, Issue 6, Pages (May 2006)

Repression of contexual fear memory induced by isoflurane is accompanied by reduction in histone acetylation and rescued by sodium butyrate T. Zhong,

Ying Li, Wei Xu, Michael W. McBurney, Valter D. Longo Cell Metabolism

Volume 42, Issue 4, Pages (April 2005)

Volume 51, Issue 6, Pages (September 2006)

Volume 10, Issue 12, Pages (December 2017)

Volume 140, Issue 2, Pages e4 (February 2011)

Volume 56, Issue 1, Pages (October 2014)

SUMO Promotes HDAC-Mediated Transcriptional Repression

Volume 60, Issue 5, Pages (November 2001)

Volume 41, Issue 5, Pages (November 2004)

Volume 18, Issue 5, Pages (January 2017)

Volume 151, Issue 1, Pages (September 2012)

Volume 77, Issue 4, Pages (February 2010)

Volume 83, Issue 3, Pages (March 2013)

Volume 59, Issue 2, Pages (August 2013)

Volume 6, Issue 4, Pages (October 2007)

Volume 3, Issue 6, Pages (December 2002)

The role of histone deacetylases in asthma and allergic diseases

Volume 119, Issue 4, Pages (October 2000)

Volume 118, Issue 1, Pages (January 2000)

SIRT1, a Class III Histone Deacetylase, Regulates LPS-Induced Inflammation in Human Keratinocytes and Mediates the Anti-Inflammatory Effects of Hinokitiol

Bo Li, Ran-Sook Woo, Lin Mei, Roberto Malinow Neuron

Volume 63, Issue 6, Pages (September 2009)

Farah D. Lubin, J. David Sweatt Neuron

LncRNA ZEB1-AS1 Was Suppressed by p53 for Renal Fibrosis in Diabetic Nephropathy Juan Wang, Jian Pang, Huiling Li, Jie Long, Fang Fang, Junxiang Chen,

Loss of Class III β-Tubulin Induced by Histone Deacetylation Is Associated with Chemosensitivity to Paclitaxel in Malignant Melanoma Cells Kiyomi Akasaka,

Volume 74, Issue 4, Pages (August 2008)

Romidepsin reduces histone deacetylase activity, induces acetylation of histones, inhibits proliferation, and activates apoptosis in immortalized epithelial.

Crotonate prevents downregulation of kidney PGC-1α and SIRT3 as well as causing CCL2 upregulation in experimental AKI. AKI was induced by a folic acid.

Mechanism of Akt1 in promoting reprogramming.

Histones acetylation is decreased in H3K9 and H3K27 in chronically mtDNA-depleted cells because of decreased HAT activity. Histones acetylation is decreased.

Histone crotonylation in kidney tubular cells.

Effect of the selective pharmacological inhibitors used.

Volume 69, Issue 2, Pages (January 2011)

Hyperthermia-induced ATF2 and NFκB phosphorylation is p38-MAPK mediated. Hyperthermia-induced ATF2 and NFκB phosphorylation is p38-MAPK mediated. The effect.

Deon G. Uffort, Elizabeth A. Grimm, Julie A. Ellerhorst

Volume 9, Issue 6, Pages (December 2017)

Volume 17, Issue 5, Pages (May 2013)

Active Repression of Antiapoptotic Gene Expression by RelA(p65) NF-κB

Volume 111, Issue 4, Pages (November 2002)

Volume 19, Issue 3, Pages (September 2010)

Inhibition of HDACs disrupts DNMT1 association with Hsp90.

Presentation transcript:

REGULATION OF HISTONE ACETYLATION IN THE HIPPOCAMPUS OF CHRONICALLY STRESSED RATS: A POTENTIAL ROLE OF SIRTUINS

In Hippocampus Chronic Variable Stress (CVS) Induces: Suppression of Synaptic Plasticity (CA1) Decreased Neurogenesis (Dentate Gyrus) Atropy in Apical Dendrites (CA3)

Histone Complex

Design Two Weeks Housed in Pairs Day 56 Chronic Variable Stress(CVS) Control Morning Stressor Overnight Stressor Afternoon Stressor Two Weeks

Fig. 2. Physiological measures of chronic stress. Quantification of physical parameters from animals subjected to either control conditions or 14 d of chronic variable stress (CVS). (A) CVS results in a significant decrease in weight gain (n=12) compared to control (n=12). (B) Serum levels of corticosterone from trunk blood are increased in CVS animals compared to control animals (n=9). (C) A significant increase in adrenal weight relative to body weight was seen in CVS animals compared to control animals (measured as mg/100 g body weight; n=12). (D) A reduction in sucrose preference was observed following CVS (measured as % sucrose intake/total fluid intake; n=6). Data are shown as means±SE; * P<0.05 vs. control; ** P<0.01 vs. control; *** P<0.0001 vs. control. Fig. 2. Physiological measures of chronic stress. Quantification of physical parameters from animals subjected to either control conditions or 14 d of chronic variable stress (CVS). (A) CVS results in a significant decrease in weight gain (n=12) compared to control (n=12). (B) Serum levels of corticosterone from trunk blood are increased in CVS animals compared to control animals (n=9). (C) A significant increase in adrenal weight relative to body weight was seen in CVS animals compared to control animals (measured as mg/100 g body weight; n=12). (D) A reduction in sucrose preference was observed following CVS (measured as % sucrose intake/total fluid intake; n=6). Data are shown as means±SE; * P<0.05 vs. control; ** P<0.01 vs. control; *** P<0.0001 vs. control. Fig. 2. Physiological measures of chronic stress. Quantification of physical parameters from animals subjected to either control conditions or 14 d of chronic variable stress (CVS). (A) CVS results in a significant decrease in weight gain (n=12) compared to control (n=12). (B) Serum levels of corticosterone from trunk blood are increased in CVS animals compared to control animals (n=9). (C) A significant increase in adrenal weight relative to body weight was seen in CVS animals compared to control animals (measured as mg/100 g body weight; n=12). (D) A reduction in sucrose preference was observed following CVS (measured as % sucrose intake/total fluid intake; n=6). Data are shown as means±SE; * P<0.05 vs. control; ** P<0.01 vs. control; *** P<0.0001 vs. control. Fig. 2. Physiological measures of chronic stress. Quantification of physical parameters from animals subjected to either control conditions or 14 d of chronic variable stress (CVS). (A) CVS results in a significant decrease in weight gain (n=12) compared to control (n=12). (B) Serum levels of corticosterone from trunk blood are increased in CVS animals compared to control animals (n=9). (C) A significant increase in adrenal weight relative to body weight was seen in CVS animals compared to control animals (measured as mg/100 g body weight; n=12). (D) A reduction in sucrose preference was observed following CVS (measured as % sucrose intake/total fluid intake; n=6). Data are shown as means±SE; * P<0.05 vs. control; ** P<0.01 vs. control; *** P<0.0001 vs. control. Fig. 2. Physiological measures of chronic stress. Quantification of physical parameters from animals subjected to either control conditions or 14 d of chronic variable stress (CVS). (A) CVS results in a significant decrease in weight gain (n=12) compared to control (n=12). (B) Serum levels of corticosterone from trunk blood are increased in CVS animals compared to control animals (n=9). (C) A significant increase in adrenal weight relative to body weight was seen in CVS animals compared to control animals (measured as mg/100 g body weight; n=12). (D) A reduction in sucrose preference was observed following CVS (measured as % sucrose intake/total fluid intake; n=6). Data are shown as means±SE; * P<0.05 vs. control; ** P<0.01 vs. control; *** P<0.0001 vs. control.

Histone Deacetylases (HDACS) Class I I II III VIII Class II VII VIII IX VI IV V X Class III Sirtuins 1 2 3 4 5 6 7 Class IV XI

Fig. 3. Histone acetylation changes in the hippocampus are subregion-specific. Quantification and representative Western blots of histone acetylation extracted from subdissected hippocampus of control and chronic variable stress (CVS) animals. (A) Immunoblotting of acetylatedhistone 4 lysine 12 [aH4(K12)] antibody showed a trend toward a decrease in the CA1 region of the hippocampus in CVS animals compared to control animals. (B) A significant decrease in acetylation of H4(K12) was observed in CA3. (C) In the dentate gyrus (DG) region of thehippocampus, CVS resulted in a significant decrease in band density of aH4(K12) acetylated antibody compared to control animals. (D, E, F) Representative Western blots of aH4(K12) and total H3 for CA3 (D), CA1 (E) and DG (F) regions of the hippocampus. (G) Western blotting of phospho-acetylation of histone 3 at lysine9/serine 10 [paH3(K9/S10)] demonstrated that levels remained unchanged in CA1. (H) A significant decrease in paH3(K9/S10) band density was observed in CA3 of CVS animals compared to control animals. (I) A significant difference in paH3(K9/S10) was observed in the DG between control and CVS animals. (J, K, L) Representative Western blots of paH3 (K9/S10) and total H3. Data are shown as means±SE; * P<0.05 vs. control (n=5–6 animals per group).

Fig. 4. Deacetylation of histones by Class I/II histone deacetylases (HDACs) in control and CVS-treated hippocampus. Western blot analysis of changes in histone 3 and histone 4 acetylation in response to HDAC inhibition in whole hippocampus slices from control and chronic variable stress (CVS) animals treated for 1-h with either vehicle or 300 μm sodium butyrate (NaB). (A) Quantification of percentage change from vehicle treated slices in acetylation of lysine 12 on histone 4 [aH4(K12)]. A significant increase from vehicle in K12H4 acetylation was observed in CVS animals compared to control animals. (B) Phospho-acetylation of lysine 9/serine 10 on histone 3 [paH3(K9/S10)] quantification of percentage change mediated by NaB compared to vehicle treated slices. No significant change from vehicle was observed in CVS animals compared to control animals. (C) Quantification and representative Western blots from nuclear protein extracted from subdissected hippocampus tissue from control and CVS animals. A significant increase in histone deacetylase 5 (HDAC5) protein expression was observed in the CA1 region of CVS animals compared to control animals with no change in either CA3 or DG. Representative Western blot of GAPDH protein expression are shown as a loading control. Data are shown as means±SE; * P<0.05 vs. control (n=4 animals per group).

Fig. 5. Inhibition of sirtuins increases histone acetylation only in chronic variable stress (CVS) treated hippocampus. Western blot analysis ofhistone acetylation extracted from whole hippocampus slices from control and chronic variable stress (CVS) animals treated for 1-h with either vehicle or 100 μm sirtinol. (A) Quantification of percentage change from vehicle treated slices in acetylation of K12H4. Pharmacological application of sirtinol resulted in a significant increase from vehicle in CVS animals compared to control animals. (B) Phospho-acetylation of K9/S10 H3 quantification of percentage change from vehicle treated slices. A significant increase from vehicle in phospho-acetylation of H3 was observed in CVS animals compared to control animals. Data are shown as means±SE; * P<0.05 vs. control; ** P<0.01 vs. control (n=4 animals per group).

Control Rat

CVS Rat

Fig. 6. Regulation of sirtuin 1 activity and protein expression in chronic stress. (A) Quantification and representative Western blots of sirtuin 1expression from nuclear protein extracted from subdissected hippocampus of control and chronic variable stress (CVS) animals. No significant difference from control animals in sirtuin 1 protein expression was seen in CA1, CA3, and DG regions in CVS animals (n=4). Representative blots from GAPDH are shown as protein loading control. (B) Quantification of Sirt 1 activity in nuclear extract from subdissected hippocampus of control and CVS animals. A significant increase in enzymatic activity of Sirt 1 was found in the CA3 and DGregions of the hippocampus of CVS animals compared to control animals. No change from control was seen in CA1 [data is represented as arbitrary florescence units (AFU) relative to control; n=4]. (C) Quantification and representative western blots of p53 acetylation relative to total p53 expression from nuclear protein extracted from subdissected hippocampus of control and CVS animals. A significant decrease in acetylation of p53 was observed in the CA3 and DG hippocampus regions of CVS animals compared to control animals while no difference from control was observed in CA1 (n=6). Data are shown as means±SE; * P<0.05 vs. control; *** P<0.0001 vs. control.

Thank you!