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PNPLA1 knockdown inhibits esterification of γ-linolenic acid to ceramide 1 in differentiated keratinocytes.
Kim, Kun-Pyo; Shin, Kyung-Oh; Lee, Sangmin; Yun, Jihyeon; Lee, Taehoon; Cho, Yunhi.
Afiliación
  • Kim KP; Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin-si, Republic of Korea.
  • Shin KO; Department of Food Science and Nutrition, Hallym University, Chuncheon-si, Republic of Korea.
  • Lee S; Department of Genetic Engineering, Kyung Hee University, Yongin-si, Republic of Korea.
  • Yun J; Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin-si, Republic of Korea.
  • Lee T; Department of Genetic Engineering, Kyung Hee University, Yongin-si, Republic of Korea.
  • Cho Y; Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin-si, Republic of Korea. Electronic address: choyunhi@khu.ac.kr.
Biochem Biophys Res Commun ; 702: 149618, 2024 04 02.
Article en En | MEDLINE | ID: mdl-38340658
ABSTRACT
Patatin-like phospholipase domain-containing 1 (PNPLA1) is crucial in the esterification of linoleic acid (LA; 182n-6) to ω-hydroxy fatty acids (FA) of ceramide 1 (Cer1), the major barrier lipid of the differentiated epidermis. We previously reported that γ-linolenic acid (GLA; 183n-6) as well as LA is esterified to Cer1 subspecies with sphingosine (d181) or eicosasphingosine (d201) amide-linked to two different ω-hydroxy FA (30wh0; 32wh1). Here, we further investigated whether PNPLA1 is also responsible for esterification of GLA to these Cer1 subspecies in normal human keratinocytes (NHK). As late/terminal differentiation was induced in NHK, PNPLA1 and differentiation markers were expressed, and LA-esterified Cer1 subspecies (182n-6/C30wh0 or C32wh0/d181; 182n-6/C32wh0/d201) were detected, which were further increased with LA treatment. GLA-esterified Cer1 subspecies (183n-6/C30wh0 or C32wh0/d181; 183n-6/C32wh0/d201) were detected only with GLA treatment. Specific small interfering RNA-mediated knockdown of PNPLA1 (KDP) in differentiated NHK decreased levels of these LA-esterified Cer1 subspecies overall and of involucrin (IVL), a terminal differentiation marker. Moreover, KDP resulted in lesser LA/GLA responses as characterized by more significant decreases in IVL and LA/GLA-esterified Cer1 subspecies overall and an accumulation of non-esterified ω-hydroxy ceramides, their putative precursors; the decrease of 183n-6/C32wh0/d181, the predominant GLA-esterified Cer1 subspecies, specifically paralleled the increase of C32wh0/d181, its corresponding precursor. PNPLA1 is responsible for NHK terminal differentiation and also for esterification of GLA to the ω-hydroxy FA of Cer1.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Queratinocitos / Ácido gammalinolénico Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Queratinocitos / Ácido gammalinolénico Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos