Inhibitors of dihydroceramide desaturase 1: Therapeutic agents and pharmacological tools to decipher the role of dihydroceramides in cell biology

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• 作者：Mireia Casasampere ; Yadira F. Ordoñ ; ez ; Ana Pou ; Josefina Casas ; ^{fina.casas@iqac.csic.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cer ; ceramide(s) ; 4-HPR ; N-(4-hydroxyphenyl)retinamide or fenretinide ; Aβ ; amyloid β peptides ; DEGS1 ; drosophila degenerative spermatocyte 1 ; DEGS2 ; drosophila degenerative spermatocyte 2 ; Des1 ; dihydroceramide desaturase 1 ; Des2 ; dihydroceramide desaturase 2 ; dhCer ; dihydroceramide(s) ; dhSo ; dihydrosphingosine ; ER ; endoplasmic reticulum ; HIV-1 ; human immunodeficiency virus 1 ; NF-κB ; nuclear factor kappa-light-chain-enhancer of activated B cells ; ROS ; reactive oxygen species ; S1P ; sphingosine 1-
• 刊名：Chemistry and Physics of Lipids
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：197
• 期：Complete
• 页码：33-44
• 全文大小：1141 K

文摘

Dihydroceramide desaturase (Des1) is the last enzyme in the de novo synthesis of ceramides (Cer). It catalyzes the insertion of a double bond into dihydroceramides (dhCer) to convert them to Cer, both of which are further metabolized to more complex (dihydro) sphingolipids. For many years dhCer have received poor attention, mainly due to their supposed lack of biological activity. It was not until about ten years ago that the concept that dhCer might have regulatory roles in biology emerged for the first time. Since then, multiple publications have established that dhCer are implicated in a wide spectrum of biological processes. Physiological and pathophysiological functions of dhCer have been recently reviewed. In this review we will focus on the biochemical features of Des1 and on its inhibition by different compounds with presumably different modes of action.