Sierra Acai Company
Sierra Acai Company
Open 7 Days a Week
MonaVie Independent Distributor
Distributor Training
Shop Online
Enroll Now
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
Friends
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
14-September-2008 18:02:39 - Histone deacetylase inhibitor Histone deacetylase inhibitors HDAC inhibitors, HDI are a class of compounds that interfere with the function of histone deacetylase. Contents 1 Cellular Biochemistry / Pharmacology 1.1 HDAC classification 1.2 Additional functions 2 Uses 3 References Cellular Biochemistry / Pharmacology To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones. This is accomplished with the assistance of histone acetylases HAT which acetylates the lysine residues in core histones leading to a less compact and more transcriptionally active chromatin, and conversely the actions of histone deacetylases HDAC which remove the acetyl groups from the lysine residues leading to the formation of a condensed and transcriptionally silenced chromatin. Reversible modification of the terminal tails of core histones constitutes the major epigenetic mechanism for remodeling higher order chromatin structure and controlling gene expression. HDAC inhibitors HDI block this action and can result in hyperacetylation of histones, therefore affecting gene expression. 1 HDAC classification HDACs are classified in four groups based on their homology to yeast histone deacetylases: Class I which includes HDAC1, -2, -3 and -8 are related to yeast RPD3 gene; Class II which includes HDAC4, -5, -6, -7, -9 and -10 are related to yeast Hda1 gene; Class III, also known as the sirtuins are related to the Sir2 gene and include SIRT1-7, and Class IV which contains only HDAC11 has features of both Class I and II. The classical HDIs act exclusively on Class I and Class II HDACs by binding to the zinc containing catalytic domain of the HDACs. These classical HDIs fall into several groupings, in order of decreasing potency: i hyroxamic acids, such as Trichostatin A, ii cyclic tetrapeptides, iii benzamides, iv electrophilic ketones, and v the aliphatic acid group of compounds such as phenylbutyrate and valproic acid.2 Second generation HDIs include SAHA approved by the FDA in 2007 for leukemia therapy under the name Vorinostat, Belinostat/PXD101, MS275, LAQ824/LBH589, CI994, and MGCD0103.3 The sirtuin Class III HDACs are NAD+ dependent and are therefore inhibited by nicotinamide, as well derivatives of NAD, dihydrocoumarin, naphthopyranone, and 2-hydroxynaphaldehydes.4 Additional functions HDIs should not be considered to act solely as enzyme inhibitors of HDACs. A large variety of nonhistone transcription factors and transcriptional co-regulators are known to be modified by acetylation. HDIs can alter the degree of acetylation nonhistone effector molecules and thereby increase or repress the transcription of genes by this mechanism. Examples include: ACTR, cMyb, E2F1, EKLF, FEN 1, GATA, HNF-4, HSP90, Ku70, NFκB, PCNA, p53, RB, Runx, SF1 Sp3, STAT, TFIIE, TCF, YY1, etc. 5 Uses HDIs have a long history of use in psychiatry and neurology as mood stabilzers and anti-epileptics. The prime example of this is valproic acid, marketed as a drug under the names of Depakene, Depakote, and Divalproex. More recently, HDIs are being studied as a mitigator neurodegenerative diseases.6 Also in recent years, there has been an effort to develop HDIs as a cancer treatment or adjunct7 The exact mechanisms by which the compounds may work are unclear, but epigenetic pathways are proposed.8 Richon et al. found that HDAC inhibitors can induce p21 WAF1 expression, a regulator of p53's tumor supressor activity HDACs are involved in the pathway by which the retinoblastoma protein pRb suppresses cell proliferation.9 The pRb protein is part of a complex which attracts HDACs to the chromatin so that it will deacetylate histones.10 HDAC1 negatively regulates the cardiovascular transcription factor Kruppel-like factor 5 through direct interaction.11 Estrogen is well-established as a mitogenic factor implicated in the tumorigenesis and progression of breast cancer via its binding to the estrogen receptor alpha ERα. Recent data indicate that chromatin inactivation mediated by HDAC and DNA methylation is a critical component of ERα silencing in human breast cancer cells.12 References ^ Thiagalingam S, Cheng KH, Lee HJ, Mineva N, Thiagalingam A, Ponte JF 2003, Histone deacetylases: unique players in shaping the epigenetic histone code. Ann N Y Acad Sci 983, 84-100. Marks PA, Richon VM, Rifkind RA 2000, Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natl Cancer Inst 92, 1210-1216. ^ Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC 2005, Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 45, 495-528. ^ Beckers T, Burkhardt C, Wieland H, et al 2007. Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int. J. Cancer 121 5: 1138-48. doi:10.1002/ijc.22751. ^ Porcu M, Chiarugi A 2005, The emerging therapeutic potential of sirtuin-interacting drugs: from cell death to lifespan extension. Trends Pharmacol Sci 26, 94-103. ^ Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC 2005, Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 45, 495-528. Yang XJ, Seto E 2007, HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene 26, 5310-5318. ^ Hahnen E, Hauke J, Tränkle C, Eyüpoglu IY, Wirth B, Blümcke I 2008, Histone deacetylase inhibitors: possible implications for neurodegenerative disorders. Expert Opin Investig Drugs 172:169-84 ^ Marks PA, Dokmanovic M 2005. Histone deacetylase inhibitors: discovery and development as anticancer agents. Expert opinion on investigational drugs 14 12: 1497-511. doi:10.1517/13543784.14.12.1497. ^ Claude Monneret April 2007. Histone deacetylase inhibitors for epigenetic therapy of cancer. Anticancer Drugs 18: 363-70. doi:10.1097/CAD.0b013e328012a5db. ^ Richon VM, Sandhoff TW, Rifkind RA, Marks PA 2000, Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proc Natl Acad Sci USA 9718:10014-10019. ^ Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T. 1998 Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 3916667:597-601. ^ Matsumura T, Suzuki T, Aizawa K, Munemasa Y, Muto S, Horikoshi M, Nagai R 2005 The deacetylase HDAC1 negatively regulates the cardiovascular transcription factor Kruppel-like factor 5 through direct interaction. J Bio Chem 28013:12123-9 ^ Zhang Z, Yamashita H, Toyama T, Sugiura H, Ando Y, Mita K, Hamaguchi M, Hara Y, Kobayashi S, Iwase H 2005, Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast. Breast Cancer Res Treat 941:11-6. Tablets This pharmacology-related article is a stub. v d e Pharmacology: enzyme inhibition Class Competitive inhibition - Uncompetitive inhibition - Non-competitive inhibition - Suicide inhibition - Mixed inhibition Substrate Oxidoreductase EC 1: Aromatase inhibitors - Lipoxygenase inhibitor - Monoamine oxidase inhibitors - COX-2 inhibitor Transferase EC 2: Integrase inhibitor - Protein kinase inhibitors - Reverse transcriptase inhibitors - COMT inhibitors Hydrolase EC 3: Acetylcholinesterase inhibitors - Phosphodiesterase inhibitors - Protease inhibitors ACE inhibitor, Trypsin inhibitor - Histone deacetylase inhibitor Lyase EC 4: Carbonic anhydrase inhibitors Retrieved from http://en..org/wiki/Histone_deacetylase_inhibitor Categories: Pharmacology stubs | Psychiatry | Neurology | Oncology Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages 中文 This page was last modified on 16 July 2008, at 11:59
39 Reasons to Drink Acai Juice Every Day
What is MonaVie - Watch the 8-minute video
Discovering MonaVie Video
The Power of You Video
Effects of MonaVie Active on Antioxidant Capacity in Humans
Log into your Wholesale MonaVie Account
So many of us do not eat a balanced diet, get enough sleep, have too much stress, or are impacted with toxins and pollutants. Drinking 2 ounces of MonaVie twice a day will help your body detoxify as well as build your immune system. Its the smartest thing you can do for yourself, so start today. Buying MonaVie through our company guarantees you support 7 days a week and, if you would like to share MonaVie with your family and friends we will guide you from start to finish.
1. Click on Enroll Now (30 - 55% off retail price)
2. Pay $39 for your Wholesale ID number.
3. NO minimum order required.
4. MonaVie is delivered to your door in 3 to 5 days.