Angiotensin II modification by decomposition products of linoleic acid-derived lipid hydroperoxide.
In: Chemico-Biological Interactions, Jg. 239 (2015-09-05), S. 87-99
academicJournal
Zugriff:
Polyunsaturated fatty acids are highly susceptible to oxidation induced by reactive oxygen species and enzymes, leading to the formation of lipid hydroperoxides. The linoleic acid (LA)-derived hydroperoxide, 13-hydroperoxyoctadecadienoic acid (HPODE) undergoes homolytic decomposition to reactive aldehydes, 4-oxo-2( E )-nonenal (ONE), 4-hydroxy-2( E )-nonenal, trans -4,5-epoxy-2( E )-decenal (EDE), and 4-hydroperoxy-2( E )-nonenal (HPNE), which can covalently modify peptides and proteins. ONE and HNE have been shown to react with angiotensin (Ang) II (DRVYIHPF) and modify the N-terminus, Arg 2 , and His 6 . ONE-derived pyruvamide-Ang II (Ang P) alters the biological activities of Ang II considerably. The present study revealed that EDE and HPNE preferentially modified the N-terminus and His 6 of Ang II. In addition to the N-substituted pyrrole of [N-C 4 H 2 ]-Ang II and Michael addition products of [His 6 (EDE)]-Ang II, hydrated forms were detected as major products, suggesting considerable involvement of the vicinal dihydrodiol (formed by epoxide hydration) in EDE-derived protein modification in vivo. Substantial amounts of [N-(EDE − H 2 O)]-Ang II isomers were also formed and their synthetic pathway might involve the tautomerization of a carbinolamine intermediate, followed by intramolecular cyclization and dehydration. The main HPNE-derived products were [His 6 (HPNE)]-Ang II and [N-(HPNE − H 2 O)]-Ang II. However, ONE, HNE, and malondialdehyde-derived modifications were dominant, because HPNE is a precursor of these aldehydes. A mixture of 13-HPODE and [ 13 C 18 ]-13-HPODE (1:1) was then used to determine the major modifications derived from LA peroxidation. The characteristic doublet (1:1) observed in the mass spectrum and the mass difference of the [M + H] + doublet aided the identification of Ang P (N-terminal α-ketoamide), [N-ONE]-Ang II (4-ketoamide), [Arg 2 (ONE − H 2 O)]-Ang II, [His 6 (HNE)]-Ang II (Michael addition product), [N-C 4 H 2 ]-Ang II (EDE-derived N-substituted pyrrole), [His 6 (HPNE)]-Ang II, [N-(9,12-dioxo-10( E )-dodecenoic acid)]-Ang II, and [His 6 (9-hydroxy-12-oxo-10( E )-decenoic acid)]-Ang II as the predominant LA-derived modifications. These modifications could represent the majority of lipid-derived modifications to peptides and proteins in biological systems. [ABSTRACT FROM AUTHOR]
Titel: |
Angiotensin II modification by decomposition products of linoleic acid-derived lipid hydroperoxide.
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Autor/in / Beteiligte Person: | Takahashi, Ryo ; Goto, Takaaki ; Oe, Tomoyuki ; Lee, Seon Hwa |
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Zeitschrift: | Chemico-Biological Interactions, Jg. 239 (2015-09-05), S. 87-99 |
Veröffentlichung: | 2015 |
Medientyp: | academicJournal |
ISSN: | 0009-2797 (print) |
DOI: | 10.1016/j.cbi.2015.06.029 |
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