Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

Abstract

Significance: Chronic obstructive pulmonary disease (COPD) is predominantly a tobacco smoke-triggered disease with features of chronic low-grade systemic inflammation and aging (inflammaging) of the lung associated with steroid resistance induced by cigarette smoke (CS)-mediated oxidative stress. Oxidative stress induces various kinase signaling pathways leading to chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation) in inflammation, senescence, and steroid resistance. Recent Advances: Histone mono-, di-, or tri-methylation at lysine residues result in either gene activation (H3K4, H3K36, and H3K79) or repression (H3K9, H3K27, and H3K20). Cross-talk occurs between various epigenetic marks on histones and DNA methylation. Both CS and oxidants alter histone acetylation/deacetylation and methylation/ demethylation leading to enhanced proinflammatory gene expression. Chromatin modifications occur in lungs of patients with COPD. Histone deacetylase 2 (HDAC2) reduction (levels and activity) is associated with steroid resistance in response to oxidative stress. Critical Issues: Histone modifications are associated with DNA damage/repair and epigenomic instability as well as premature lung aging, which have implications in the pathogenesis of COPD. HDAC2/SIRTUIN1 (SIRT1)-dependent chromatin modifications are associated with DNA damage-induced inflammation and senescence in response to CS-mediated oxidative stress. Future Directions: Understanding CS/oxidative stress-mediated chromatin modifications and the cross-talk between histone acetylation and methylation will demonstrate the involvement of epigenetic regulation of chromatin remodeling in inflammaging. This will lead to identification of novel epigenetic-based therapies against COPD and other smoking-related lung diseases. Pharmacological activation of HDAC2/SIRT1 or reversal of their oxidative post-translational modifications may offer therapies for treatment of COPD and CS-related diseases based on epigenetic histone modifications.

Association of Airflow Limitation With Carotid Atherosclerosis in a Japanese Community ― The Hisayama Study ―

“…In addition, there may be other underlying mechanisms, such as oxidative stress. 25 Clinical and experimental studies have shown that the production of reactive oxygen species (ROS) is increased in COPD patients by inhalation of toxic substances, [26][27][28] and that the antioxidative system in these patients is impaired, 29 leading to a state of high oxidative stress. After such an increase in ROS production, the spillover of ROS from the lung could lead to systemically increased levels of oxidative stress.…”

Comparative Effects of Roystonea Regia (D-004) and Saw Palmetto Lipid Extracts On Blood Oxidative Variables in Men with Benign Prostate Hyperplasia (BPH)

“…Despite smoking increases the extent of OS [37,38] and may contribute to BPH risk, although not clearly [39], we did not exclude smokers because we wanted to compare the effects of D-004 and SP in conditions near to routine practice, in which smoking unfortunately this habit is common. The frequency of smokers was relatively high (12 of 48 randomized subjects, 25%), but similar in both groups, so that this factor had no impact on the comparative results.…”

Novel biomarker candidates for the diagnosis of ovarian clear cell carcinoma

“…Chromatin remodeling may be important for the repair of DNA damage in oxidative lesions, in order to maintain genome stability (65). Components of the chromatin remodeling multiprotein complexes may harbor develop gene sequence mutations that lead to protein inactivation or loss of expression in various types of human cancer, including ovarian clear cell carcinoma (66).…”