Artículo
TAG synthesis and storage under osmotic stress. A requirement for preserving membrane homeostasis in renal cells
Weber, Karen
; Casali, Cecilia Irene
; Gaveglio, Virginia Lucía
; Pasquaré, Susana Juana; Morel Gómez, Emanuel Dario
; Parra, Leandro Gastón
; Erjavec, Luciana Cecilia
; Perazzo, Cecilia; Fernandez, Maria del Carmen
Fecha de publicación:
14/09/2018
Editorial:
Elsevier Science
Revista:
Biochimica Et Biophysica Acta - Molecular and Cell Biology of Lipids
ISSN:
1388-1981
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Hyperosmolarity is a controversial signal for renal cells. It can induce cell stress or differentiation and both require an active lipid metabolism. We showed that hyperosmolarity upregulates phospholipid (PL) de novo synthesis in renal cells. PL synthesis requires fatty acids (FA), usually stored as triglycerides (TAG). PL and TAG de novo synthesis utilize the same initial biosynthetic route: sn-glycerol 3P (G3P) → phosphatidic acid (PA) → diacylglycerol (DAG). In the present work, we evaluate how such pathway contributes to PL and TAG synthesis in renal cells subjected to hyperosmolarity. Our results show an increase in PA and DAG formation under hyperosmotic conditions; augmented DAG production, due to lipin enzyme activity, lead to the increase of both TAG and PL. However, at early stages (24 and 48 h), most of the de novo synthesized DAG was directed to PL synthesis; longer treatments downregulated PL synthesis and the DAG formed was mainly driven to TAG synthesis. Hyperosmolarity induced ACC and FASN transcription which mediated FA de novo synthesis. New FA molecules were stored in TAG. Silencing experiments revealed that hyperosmotic-induction of lipin-1 and -2 was mediated by SREBP1. Interestingly, SREBP1 knockdown also dropped SREBP2, indicating a modulatory action between both isoforms. Impairing SREBP activity leads to a decline in TAG levels but not PL. Membrane homeostasis is maintained through the adequate PL synthesis and renewal and constitute a protective mechanism against hyperosmolarity. The present data reveal the relevance of TAG synthesis and storage for PL synthesis in renal cells.
Palabras clave:
DGAT
,
HYPEROSMOLARITY
,
LIPIN
,
PHOSPHOLIPID SYNTHESIS
,
SREBP
,
TRIGLYCERIDE STORAGE
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Colecciones
Articulos(INIBIBB)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
Weber, Karen; Casali, Cecilia Irene; Gaveglio, Virginia Lucía; Pasquaré, Susana Juana; Morel Gómez, Emanuel Dario; et al.; TAG synthesis and storage under osmotic stress. A requirement for preserving membrane homeostasis in renal cells; Elsevier Science; Biochimica Et Biophysica Acta - Molecular and Cell Biology of Lipids; 1863; 9; 14-9-2018; 1108-1120
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