Seminar Series-DEPARTMENT OF BIOCHEMISTRY & MOLECULAR BIOLOGY

Dr. Irfan Rahman

Professor of Environmental, Pulmonary Medicine, and Public Health Sciences
University of Rochester, NY

OXIDATIVE STRESS, CHROMATIN REMODELING, AND CELLULAR SENESCENCE IN LUNG INFLAMMATION

Department of Environmental Medicine and Medicine (Pulmonary), University of Rochester Medical Center, Rochester, NY.

Oxidative stress, chronic inflammation and cellular senescence are important contributing factors in inflammaging. Cellular senescence (stress-induced) is a form of irreversible growth arrest. The molecular mechanism of stress-induced cellular senescence in premature aging and in the pathogenesis of various chronic inflammatory diseases, such as Chronic Obstructive Pulmonary Disease (COPD) is not known. Chromatin modifications (histone acetylation/deacetylation and methylation/demethylation) occur during the establishment of cellular senescence associated with inflammatory response. Histone deacetylase 2 (HDAC2) is known to regulate DNA damage/repair and cellular senescence, and its level is significantly reduced in response to oxidative/carbonyl stress in lung cells. This reduction is associated with specific changes in histone H3 acetylation via kinase-CBP/p300 signaling and methylation. Mice deficient in HDAC2 exhibit augmented DNA damage, impaired DNA non-homologous end joining (NHEJ) repair, cellular senescence and inflammatory response in lungs in response to cigarette smoke exposure. Sirtuin1 (SIRT1), an anti-aging protein, attenuates cigarette smoke-induced lung inflammation and injury. SIRT1 regulates cellular senescence via regulating FOXO3, p53, and NF-κB, oxidative stress (antioxidant genes), as well as various proteins/coactivators involved in DNA damage and repair. Oxidant/carbonyl reduces SIRT1 level and activity, which results in acetylation of target proteins, such as p53, RelA/p65 and FOXO3, thereby leading to increased inflammatory response, cellular senescence and apoptosis. We have recently shown that defective mitophagy is associated with stress-induced cellular senescence. Various signaling molecular pathways/targets and chromatin modifications involved in stress-induced cellular senescence in the pathogenesis of chronic airway disease will be presented.

 

Monday, August 31, 2015 at 12:00pm to 1:00pm

DRC, 1002

Event Type

Research

Audience

Faculty and Staff

College/Department

College of Medicine, Biochemistry and Molecular Biology

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