title: Occurrence of cytotoxic 9-oxononanoyl secosterol aldehydes in human low-density lipoprotein.
abstract: The reaction products of three major cholesteryl esters, cholesteryl palmitate (C16:0-CE), cholesteryl oleate (C18:1-CE), and cholesteryl linoleate (C18:2-CE), present in human low-density lipoprotein (LDL) treated with ozone were isolated and characterized. In vitro ozonization of C16:0-CE was found to form the palmitoyl ester of secosterol-A (3β-hydroxy-5-oxo-5,6-secocholestan-6-al) and its aldolization product secosterol-B (3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxaldehyde). On the other hand, when C18:1-CE and C18:2-CE were oxidized by ozone, the aldehyde 9-oxononanoyl cholesterol (9-ONC) was formed as a primary product, which was then further oxidized to form 9-oxononanoyl secosterol-A (9-ON-secoA) and 9-oxononanoyl secosterol-B (9-ON-secoB). The compounds 9-ON-secoA and -B, but not 9-ONC, were found to exhibit strong cytotoxicity against human leukemia HL-60 cells. An LC-ESI-MS/MS method was developed for the detection of these cholesteryl ester ozonolysis products by derivatizing them with dansyl hydrazine. Using this method, we found for the first time that low concentrations of 9-ON-secoA and -B, but not palmitoyl secosterols, were present in human LDL. These novel oxidized cholesterol esters, 9-ON-secoA and -B, probably play important roles in the pathogenesis of several inflammatory disorders such as cancer, diabetes, atherosclerosis, and neurodegenerative diseases.
authors: Laboratory of Biochemistry, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, Graduate Program in Food and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan. miyoshin@u-shizuoka-ken.ac.jp
authors: Noriyuki
authors: N
authors: Miyoshi
authors: Nozomi
authors: N
authors: Iwasaki
authors: Susumu
authors: S
authors: Tomono
authors: Tatsuya
authors: T
authors: Higashi
authors: Hiroshi
authors: H
authors: Ohshima
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002778:Cholestanones / Q000737:chemistry; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002788:Cholesterol Esters / Q000737:chemistry / Q000302:isolation & purification; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000032:analysis / Q000737:chemistry*; D010084:Oxidation-Reduction; D010126:Ozone / Q000737:chemistry; D012632:Secosteroids / Q000737:chemistry
chemical_list: C114702:9-oxononanoyl cholesterol; D000447:Aldehydes; D002778:Cholestanones; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D012632:Secosteroids; C014409:cholesteryl oleate; C021976:cholesteryl linoleate; D010126:Ozone; C082684:3-hydroxy-5-oxo-5,6-secocholestan-6-al; D002784:Cholesterol; C026651:cholesteryl palmitate