Double di oxygenation by mouse 8S-lipoxygenase: Specific formation of a potent peroxisome proliferator-activated receptor {alpha} agonist

Journal Article · Fri Dec 09 00:00:00 EST 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2005.0· OSTI ID:20793190

Jisaka, Mitsuo ^[1]; Iwanaga, Chitose ^[1]; Takahashi, Nobuyuki ^[2]; Goto, Tsuyoshi ^[2]; Kawada, Teruo ^[2]; Yamamoto, Tatsuyuki ^[1]; Ikeda, Izumi ^[1]; Nishimura, Kohji ^[1]; Nagaya, Tsutomu ^[1]; Fushiki, Tohru ^[2]; Yokota, Kazushige ^[1]

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1. Department of Life Science and Biotechnology, Shimane University, Matsue, Shimane 690-8504 (Japan)
2. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502 (Japan)

Mouse 8S-lipoxygenase (8-LOX) metabolizes arachidonic acid (AA) specifically to 8S-hydroperoxyeicosatetraenoic acid (8S-HPETE), which will be readily reduced under physiological circumstances to 8S-hydroxyeicosatetraenoic acid (8S-HETE), a natural agonist of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}). Here, we investigated whether 8-LOX could further oxygenate AA and whether the products could activate PPARs. The purified recombinant 8-LOX converted AA exclusively to 8S-HPETE and then to (8S,15S)-dihydroperoxy-5Z,9E,11Z,13E-eicosatetraenoic acid (8S,15S-diHPETE). The k {sub cat}/K {sub m} values for 8S-HPETE and AA were 3.3 x 10{sup 3} and 2.7 x 10{sup 4} M{sup -1} s{sup -1}, respectively. 8-LOX also dioxygenated 8S-HETE and 15S-H(P)ETE specifically to the corresponding 8S,15S-disubstituted derivatives. By contrast, 15-LOX-2, a human homologue of 8-LOX, produced 8S,15S-diH(P)ETE from 8S-H(P)ETE but not from AA nor 15S-H(P)ETE. 8S,15S-diHETE activated PPAR{alpha} more strongly than 8S-HETE did. The present results suggest that 8S,15S-diH(P)ETE as well as 8S-H(P)ETE would contribute to the physiological function of 8-LOX and also that 8-LOX can function as a potential 15-LOX.

• OSTI ID: 20793190
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 338, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.08.029; PII: S0006-291X(05)01725-0; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARACHIDONIC ACID
MICE
NUCLEAR MAGNETIC RESONANCE
RADIONUCLIDE KINETICS
RECEPTORS
SULFUR IONS