Oxidative stress-mediated chemical modifications to biomacromolecules: Mechanism and implication of modifications to human skin keratins and angiotensin II

研究成果: Review article査読

2 被引用数 (Scopus)

抄録

Dysregulated production of reactive oxygen species (ROS) during oxidative stress has been associated with a number of inflammatory and age-related degenerative diseases. ROS can directly react with DNA to form oxidized DNA bases. Direct protein oxidation and carbonylation occur on certain amino acid residues resulting in various post-translational modifications. ROS can also initiate the formation of lipid hydroperoxides, which undergo homolytic decomposition to the α,β-unsaturated aldehydic bifunctional electrophiles such as 4-oxo-2(E)-nonenal (ONE) and 4-hydroxy-2 (E)-nonenal (HNE). Intracellular generation of highly reactive aldehydes can then result in the formation of DNA and protein adducts. ONE-derived heptanone-etheno and HNE-derived propano DNA adducts have been detected and shown to be mutagenic in a variety of biological systems. In addition, ONE and HNE are involved in protein dysfunctions and altered gene regulations through the modification of amino acid residues and crosslinking of proteins. Our recent study on human skin keratins has identified specific K1 methionine residues as the most susceptible sites to oxidation with hydrogen peroxide, which can be potential biomarkers of oxidative skin damage. The reactions of angiotensin (Ang) II with ONE or HNE produced several modified Ang IIs including a novel pyruvamide-Ang II that formed via oxidative decarboxylation of N-terminal aspartic acid. Subsequently, it has been revealed that the oxidative modifications on the N-terminus of Ang II disrupt interactions with Ang II type 1 receptor and aminopeptidase A, which could affect the regulation of cardiovascular function.

本文言語English
ページ(範囲)1055-1065
ページ数11
ジャーナルYakugaku Zasshi
133
10
DOI
出版ステータスPublished - 2013

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

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