Acrolein Induces Mitochondrial DNA Damages and Mutations in Human Lung Cells

• Main Authors: Jing-Heng Lin, 林敬恒
• Other Authors: Hsiang-Tsui Wang
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/q89a72

碩士 === 國立陽明大學 === 藥理學研究所 === 105 === Acrolein (Acr), an α,β-unsaturated aldehyde, is a ubiquitous environmental pollutant and it also generated during cellular metabolism results in various health problems including lung diseases. Tobacco smoke, car exhausts, and even overheated vegetable and animal fats are the major sources, which are also known to be involved in lung diseases including lung cancer. It shows high reactivity with cellular nucleophiles such as DNA, RNA, proteins and phospholipids. Acr can cross-linked to DNA bases forming α- and γ- hydroxy-1,N2-cyclic propano-deoxyguanosine DNA adducts (α and γ-HOPdG). Our previous results have shown Acr can react with DNA forming mutagenic DNA adducts in nuclear DNA (nDNA) and it also enhances mutagenicity of oxidative DNA damages through impairment of DNA repair function. However, the effect of Acr on mitochondrial DNA (mtDNA) remains unclear. The purpose of this study is to understand the role of acrolein in mtDNA damage, mutation and mitochondrial homeostasis. In the present study, we found that Acr-induced oxidative stress causes inhibition of mitochondrial bioenergetics, mtDNA damages, alteration of mtDNA copy number, influences mtDNA gene expression and also induces mtDNA 4977 bp deletion in human lung cells. Furthermore, mitophagy induced by Acr fails to remove Acr-induced mtDNA damage in human lung cells. Together, these data link Acr-mediated mtDNA damage, altered gene expression, mutations and mitochondrial dysfunction in lung cells. This research may help understand the role of Acr in mtDNA integrity and provide the insight for prevention of Acr-induced lung diseases.