Role of histone deacetylase 2 in epigenetics and cellular senescence: implications in lung inflammaging and COPD

Am J Physiol Lung Cell Mol Physiol. 2012 Oct 1;303(7):L557-66. doi: 10.1152/ajplung.00175.2012. Epub 2012 Jul 27.

Abstract

Histone deacetylase 2 (HDAC2) is a class I histone deacetylase that regulates various cellular processes, such as cell cycle, senescence, proliferation, differentiation, development, apoptosis, and glucocorticoid function in inhibiting inflammatory response. HDAC2 has been shown to protect against DNA damage response and cellular senescence/premature aging via an epigenetic mechanism in response to oxidative stress. These phenomena are observed in patients with chronic obstructive pulmonary disease (COPD). HDAC2 is posttranslationally modified by oxidative/carbonyl stress imposed by cigarette smoke and oxidants, leading to its reduction via an ubiquitination-proteasome dependent degradation in lungs of patients with COPD. In this perspective, we have discussed the role of HDAC2 posttranslational modifications and its role in regulation of inflammation, histone/DNA epigenetic modifications, DNA damage response, and cellular senescence, particularly in inflammaging, and during the development of COPD. We have also discussed the potential directions for future translational research avenues in modulating lung inflammaging and cellular senescence based on epigenetic chromatin modifications in diseases associated with increased oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Animals
  • Cellular Senescence / genetics*
  • DNA Damage / genetics
  • DNA Repair / genetics
  • Epigenesis, Genetic*
  • Histone Deacetylase 2 / genetics
  • Histone Deacetylase 2 / physiology*
  • Histones / metabolism
  • Humans
  • Mice
  • Oxidative Stress / genetics
  • Pneumonia / drug therapy
  • Pneumonia / genetics*
  • Pneumonia / metabolism
  • Protein Processing, Post-Translational / genetics
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Rats
  • Smoking / adverse effects
  • Smoking / genetics
  • Smoking / metabolism

Substances

  • Adrenal Cortex Hormones
  • Histones
  • Histone Deacetylase 2