Faculty Collaboration Database

Photodynamically generated 3-beta-hydroxy-5 alpha-cholest-6-ene-5- hydroperoxide: toxic reactivity in membranes and susceptibility to enzymatic detoxification. Photochem Photobiol 1995 Sep;62(3):580-7

Date

09/01/1995

Pubmed ID

8570716

DOI

10.1111/j.1751-1097.1995.tb02388.x

Scopus ID

2-s2.0-0028890784 (requires institutional sign-in at Scopus site)   36 Citations

Abstract

Singlet oxygen (1O2)-mediated photooxidation of cholesterol gives three hydroperoxide products: 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha-OOH), 3 beta-hydroxycholest-4-ene-6 alpha-hydroperoxide (6 alpha-OOH) and 3 beta-hydroxycholest-4-ene-6 beta-hydroperoxide (6 beta-OOH). These species have been compared with respect to photogeneration rate on the one hand and susceptibility to enzymatic reduction/detoxification on the other, using the erythrocyte ghost as a cholesterol-containing test membrane and chloroaluminum phthalocyanine tetrasulfonate (AlPcS4) as a 1O2 sensitizer. Peroxide analysis was accomplished by high-performance liquid chromatography with mercury cathode electrochemical detection (HPLC-EC[Hg]). The initial rate of 5 alpha-OOH accumulation in AlPcS4/light-treated ghosts was found to be about three times greater than that of 6 alpha-OOH or 6 beta-OOH. Membranes irradiated in the presence of ascorbate and ferric-8-hydroxyquinoline (Fe[HQ]2, a lipophilic iron complex) accumulated lesser amounts of 5 alpha-OOH, 6 alpha-OOH and 6 beta-OOH but relatively large amounts of another peroxide pair, 3 beta-hydroxycholest-5-ene-7 alpha- and 7 beta-hydroperoxide (7 alpha, 7 beta-OOH), suggestive of iron-mediated free radical peroxidation. When photoperoxidized membranes containing 5 alpha-OOH, 6 alpha,6 beta-OOH and 7 alpha,7 beta-OOH (arising from 5 alpha-OOH rearrangement) were incubated with glutathione (GSH) and phospholipid hydroperoxide glutathione peroxidase (PHGPX), all hydroperoxide species underwent HPLC-EC(Hg)-detectable reduction to alcohols, the relative first order rate constants being as follows: 1.0 (5 alpha-OOH), 2.0 (7 alpha,7 beta-OOH), 2.4 (6 alpha-OOH) and 3.2 (6 beta-OOH).(ABSTRACT TRUNCATED AT 250 WORDS)

Author List

Geiger PG, Korytowski W, Girotti AW

Author

Albert W. Girotti PhD Adjunct Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cholesterol
Erythrocyte Membrane
Humans
Inactivation, Metabolic
Leukemia L1210
Lipid Peroxides
Mice
Oxidation-Reduction
Photochemistry
Tumor Cells, Cultured