Kansai Photon Science Institute >> KPSI Seminar >> Oxidative Damage to Macromolecules in Carcinogenesis and Atherogenesis
Seminar
The 48th KPSI Seminar
Oxidative Damage to Macromolecules in Carcinogenesis and Atherogenesis
| Presentor | NAKAMURA Jun, D.V.M., Ph.D. （Laboratory of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University） |
|---|---|
| Place | ITBL G201 room (KPSI） |
| Date | 13:15 - (WED) Jan. 16, 2019 |
| abstract | [PDFfile／199KB] |
Oxidative Damage to Macromolecules in Carcinogenesis and Atherogenesis
NAKAMURA Jun, D.V.M., Ph.D.
（Laboratory of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University）
abstract
DNA and protein damage induced by oxidative stress is associated with various different human pathologies, such as cancer and atherosclerosis. Although, the DNA oxidation product 8-oxodG is one of the most popular biomarkers in oxidative stress and a potent pre-mutagenic lesion, the biological importance of 8-oxodG in carcinogenesis needs further investigation. Unexpectedly, our study uncovered that hydrogen peroxide causes an increase in oxidative clustered DNA lesions (OCDLs) with a significant elevation of replication-independent double strand breaks (DSBs). We also demonstrated a significant contribution of the non-homologous end joining (NHEJ) pathway in hydrogen peroxide-induced DNA repair & mutagenesis. This genomic instability induced by low levels of ROS may be involved in the etiology of a wide variety of human diseases like chronic inflammation-related disorders, carcinogenesis, neurodegeneration and aging. In addition to DNA, protein is also a target of oxidative stress. Our recent study found that fluorescent malondialdehyde-formaldehyde (M2FA)-lysine adducts are generated during atherogenesis in mice. M2FA is a strong immunogenic adduct without adjuvants in mice. Natural antibody titers against M2FA are elevated in atherosclerosis-prone mice. Our results strongly suggest that the 1,4-dihydropyridine-type of lysine adducts observed in atherosclerosis lesions are likely produced by endogenous formaldehyde and malondialdehyde with lysine. These highly fluorescent M2FA adducts may play important roles in human inflammatory and degenerative diseases.
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