Dysfunction of proteasome and pathogenesis in age-related disorders

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460489
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: Tomaru Utano 北海道大学, 医学(系)研究科(研究院), 准教授 (20360901)
• Co-Investigator(Kenkyū-buntansha): ISHIZU AKIHIRO 北海道大学, 大学院保健科学研究院, 教授 (60321957)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: プロテアソーム / 老化 / 老化関連疾患 / 細胞ストレス / 肺気腫

Outline of Final Research Achievements

The proteasome plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by cellular stresses. Proteasome activity decreases with aging in many organs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

Free Research Field

実験病理