Chemical and apoptotic properties of hydroxy-ceramides containing long-chain bases with unusual alkyl chain lengths.
We analysed four types of free ceramides (Cer 1, Cer 2, Cer 3 and Cer 4) from equine kidneys by electrospray ionization mass spectrometry. Cer 1 was composed of dihydroxy long-chain bases (dLCBs) of (4E)-sphingenine (d18:1), sphinganine and non-hydroxy fatty acids (NFAs); Cer 2 was composed of trihydroxy LCBs (tLCBs) of 4-hydroxysphinganine, t16:0, t18:0, t19:0 and t20:0, and NFAs; Cer 3 was composed of dLCBs, d16:1, d17:1, d18:1, d19:1 and d20:1, and hydroxy FAs (HFAs); and Cer 4 was composed of tLCBs, t16:0, t17:0, t18:0, t19:0 and t20:0, and HFAs. The results indicate all ceramide species containing LCBs with non-octadeca lengths (NOD-LCBs) can be classified into hydroxy-ceramides since these species always consist of tLCBs, and/or HFAs. Furthermore, such species tend to contain FAs with longer acyl chains but contain neither palmitate (C16:0) nor its hydroxylated form (C16:0h). The apoptosis-inducing activities of these hydroxyl-ceramides towards tumour cell lines were compared with that of non-hydroxy-ceramides, dLCB-NFA (Cer 1). Monohydroxy-ceramides, tLCB-NFA (Cer 2) and dLCB-HFA (Cer 3), exhibited stronger activities, whereas dihydroxy-ceramides, tLCB-HFA (Cer 4), exhibited similar or weaker activity than dLCB-NFA (Cer 1), depending on cell lines.
Kyogashima
Mamoru
M
Division of Molecular Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan. mkyogashi@aichi-cc.jp
Tadano-Aritomi
Keiko
K
Aoyama
Toshifumi
T
Yusa
Akiko
A
Goto
Yoshiko
Y
Tamiya-Koizumi
Keiko
K
Ito
Hiromi
H
Murate
Takashi
T
Kannagi
Reiji
R
Hara
Atsushi
A
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002518:Ceramides / Q000096:biosynthesis / Q000737:chemistry* / Q000633:toxicity; D005227:Fatty Acids / Q000032:analysis; D006736:Horses; D006801:Humans; D007668:Kidney / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
D002518:Ceramides; D005227:Fatty Acids