A possible role for plasmalogens in protecting animal cells against photosensitized killing.
Chinese hamster ovary (CHO) cells incorporate 12-(1'-pyrene) dodecanoic acid (P12) into membrane lipids. Exposure of P12-labeled cells to long wavelength ultraviolet light causes cell killing, presumably because excitation of the pyrene moiety (a photosensitizer) leads to the generation of reactive oxygen species. Cytotoxicity is dependent upon the concentration of P12 used to label the cells, and time of UV exposure, and the presence of oxygen during irradiation. CHO mutant cells deficient in plasmalogen biosynthesis and peroxisome assembly (Zoeller, R.A., and Raetz, C.R.H. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5170-5174) are several orders of magnitude more sensitive to P12/UV treatment than wild-type cells, permitting direct selection of one wild-type cell in 1 X 10(4) mutant cells. A major factor responsible for the P12/UV hypersensitivity of these mutants appears to be the absence of plasmalogens. Supplementation of the mutants with 1-O-hexadecyl-sn-glycerol restores plasmalogen levels and nearly normal resistance to P12/UV treatment, whereas the biogenesis of peroxisomes is not restored. The P12/UV hypersensitivity of the plasmalogen-deficient mutants, together with the selective, P12/UV-induced decomposition of plasmalogens in wild-type cells, documented in the accompanying manuscript, suggest that the vinyl ether linkage of plasmalogens plays a direct role in protecting animal cell membranes against certain oxidative stresses.
Zoeller
R A
RA
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison 53706.
Morand
O H
OH
Raetz
C R
CR
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D008856:Microscopy, Fluorescence; D009154:Mutation; D010955:Plasmalogens / Q000378:metabolism / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D010955:Plasmalogens; D011838:Radiation-Sensitizing Agents; C020791:phosphatidal ethanolamines