Τίτλος:
Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Cytokines are pivotal mediators of the immune response, and their coordinated expression protects host tissue from excessive damage and oxidant stress. Nevertheless, the development of lung pathology, including asthma, chronic obstructive pulmonary disease, and ozone-induced lung injury, is associated with oxidant stress; as evidence, there is a significant increase in levels of the modified guanine base 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. 8-OxoG is primarily recognized by 8-oxoguanine glycosylase 1 (OGG1), which catalyzes the first step in the DNA base excision repair pathway. However, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, including NF-κB, to their cognate sites to enable expression of cytokines and chemokines, with ensuing recruitments of inflammatory cells. Hence, defective OGG1 will modulate the coordination between innate and adaptive immunity through excessive oxidant stress and cytokine dysregulation. Both oxidant stress and cytokine dysregulation constitute key elements of oncogenesis by KRAS, which is mechanistically coupled to OGG1. Thus, analysis of the mechanism by which OGG1 modulates gene expression helps discern between beneficial and detrimental effects of oxidant stress, exposes a missing functional link as a marker, and yields a novel target for lung cancer. © 2018 Elsevier Inc.
Συγγραφείς:
Vlahopoulos, S.
Adamaki, M.
Khoury, N.
Zoumpourlis, V.
Boldogh, I.
Περιοδικό:
Pharmacology and Therapeutics
Εκδότης:
ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
Λέξεις-κλειδιά:
8 oxoguanine glycosylase 1; DNA ligase; immunoglobulin enhancer binding protein; Ras protein; reactive oxygen metabolite; unclassified drug; DNA glycosyltransferase; immunoglobulin enhancer binding protein; oxoguanine glycosylase 1, human; reactive oxygen metabolite, cancer prognosis; enzyme activity; gene expression; human; immunopathology; innate immunity; lung cancer; lung carcinogenesis; lung parenchyma; non small cell lung cancer; nonhuman; pneumonia; priority journal; Review; animal; immunology; innate immunity; lung tumor; prognosis, Animals; DNA Glycosylases; Humans; Immunity, Innate; Lung Neoplasms; NF-kappa B; Prognosis; Reactive Oxygen Species
DOI:
10.1016/j.pharmthera.2018.09.004
