title: Mechanisms of enhanced apoptosis in HL-60 cells by UV-irradiated n-3 and n-6 polyunsaturated fatty acids.
abstract: We examined the effects of arachidonic acid (AA), eicosapentaenoic acid (EPA), and their ultraviolet (UV)-irradiated products on HL-60 cells and isolated mitochondria to explore the following four obscure points in the mechanism of polyunsaturated fatty acids (PUFAs)-induced apoptosis: (i). the role of reactive oxygen species, (ii). the interaction of PUFAs and their metabolites with mitochondria in situ, (iii). the cyclosporine A (CsA)-sensitivity in PUFA-induced membrane permeability transition, (iv). the specificity of oxidized n-3 PUFAs in the induction of apoptosis in cancer cells. UV-oxidized PUFAs contained conjugated dienes and thiobarbituric acid reactive substances (TBARS). The apoptotic effects of PUFAs on HL-60 cells were increased by UV-irradiation whereas the swelling effect of PUFAs on isolated mitochondria was decreased. Both oxidized n-3 and n-6 PUFAs induced increased depolarization, ferricytochrome c release, the activation of various caspases, and DNA-fragmentation in a CsA-insensitive mechanism concomitant with a slight increase in the value of TBARS in cells. Furthermore, there were no significant differences in the mechanism of apoptosis induced by either oxidized AA or oxidized EPA. On the basis of these results, it was concluded that both oxidized n-3 or n-6 PUFAs induced apoptosis in HL-60 cells by a similar mechanism in a CsA-insensitive manner and also that oxidized products of PUFAs, but not the cellular oxidation process itself, play an important role in the mechanism of apoptosis in HL-60 cells.
authors.affiliation: Institute of Medical Science, Kurashiki Medical Center, Kurashiki, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Arita
authors.forename: Yorihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takehara
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Utsumi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kanno
authors.forename: Chosei
authors.initials: C
authors.lastname: Miyaguchi
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Akiyama
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Kozo
authors.initials: K
authors.lastname: Utsumi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology* / Q000528:radiation effects*; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C494816:Bid protein, rat; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D005231:Fatty Acids, Unsaturated; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D016572:Cyclosporine; D045304:Cytochromes c; D015118:Eicosapentaenoic Acid; D020169:Caspases