Cairns, Rose and Alvarez-Guaita, Anna and Martinez-Saludes, Ines and Wason, Sundeep J. and Hanh, Jacky and Nagarajan, Shilpa R. and Hosseini-Beheshti, Elham and Monastyrskaya, Katia and Hoy, Andrew J. and Buechler, Christa and Enrich, Carlos and Rentero, Caries and Grewal, Thomas (2017) Role of hepatic Annexin A6 in fatty acid-induced lipid droplet formation. EXPERIMENTAL CELL RESEARCH, 358 (2). pp. 397-410. ISSN 0014-4827, 1090-2422
Full text not available from this repository. (Request a copy)Abstract
Annexin A6 (AnxA6) has been implicated in the regulation of endo-/exocytic pathways, cholesterol transport, and the formation of multifactorial signaling complexes in many different cell types. More recently, AnxA6 has also been linked to triglyceride storage in adipocytes. Here we investigated the potential role of AnxA6 in fatty acid (FA) induced lipid droplet (LD) formation in hepatocytes. AnxA6 was associated with LD from rat liver and HuH7 hepatocytes. In oleic acid (OA) -loaded HuH7 cells, substantial amounts of AnxA6 bound to LD in a Ca2+-independent manner. Remarkably, stable or transient AnxA6 overexpression in HuH7 cells led to elevated LD numbers/size and neutral lipid staining under control conditions as well as after OA loading compared to controls. In contrast, overexpression of AnxAl, AnxA2 and AnxA8 did not impact on OA-induced lipid accumulation. On the other hand, incubation of AnxA6-depleted HuH7 cells or primary hepatocytes from AnxA6 KO-mice with OA led to reduced FA accumulation and LD numbers. Furthermore, morphological analysis of liver sections from A6-KO mice revealed significantly lower LD numbers compared to wildtype animals. Interestingly, pharmacological inhibition of cytoplasmic phospholipase Ala (cPLA(2)alpha)-dependent LD formation was ineffective in AnxA6-depleted HuH7 cells. We conclude that cPLA(2)alpha-dependent pathways contribute to the novel regulatory role of hepatic AnxA6 in LD formation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHOLESTEROL TRANSPORT; PHOSPHOLIPASE A(2); PROTEINS; MICE; DEGRADATION; TRAFFICKING; AUTOPHAGY; GOLGI; LIVER; VI; Annexin A6; Lipid droplets; Fatty acid; Hepatocytes; Cytoplasmic phospholipase A2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:15 |
| Last Modified: | 14 Feb 2019 09:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1181 |
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