Association of SND1 protein to low density lipid droplets in liver steatosis
Although the human homologue of SND p102, p100 coactivator, was initially described as a nuclear protein, the p100 coactivator protein family members have non-nuclear localization in mammalian cells with active lipid handling, storage, and secretion. However, their role in lipid homeostasis remains unresolved. Here, we investigate the distribution of the rat homologue SND p102 (also called SND1) and its association with newly formed lipid droplets in the liver parenchyma and cultured hepatocytes. Sucrose gradient fractionation showed that SND p102 cofractionated with endoplasmic reticulum and Golgi markers. Such cofractionation was not altered in regenerating steatotic rat liver. However, SND p102 was also detected in lipid droplets from regenerating liver, showing a specific directionalization to the least dense ones. Confocal microscopy of cultured hepatocytes confirmed the findings of gradient fractionation. In addition, p100 coactivator was consistently encountered in microsomes and lipid droplets in control and oleate-treated HepG2 cells. The total amount of SND p102 in hepatocytes was similar in both conditions, suggesting a specific translocation of the protein. Our findings indicate that SND p102 and the human p100 coactivator have a ubiquitous cytoplasmic distribution in hepatocytes and that steatogenic conditions promote the targeting of SND p102 from other cell compartments to specific low density lipid droplets.
KeywordsSND p102 SND1 Lipid droplets Hepatocytes Hepatic steatosis
The authors wish to thank C. Enrich for his contribution in the initial stage of this work and M. Busto for her excellent technical assistance. This research was supported by the Spanish Ministry of Education and Science (SAF2007-60211), Basque Government (PE06UN24 and IT-325-07) and the University of the Basque Country (15942/2004). Y.R. is recipient of a FPI fellowship from the Basque Government.
- 9.Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF (2006) Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res 5:3135–3144CrossRefPubMedGoogle Scholar
- 13.Fujimoto Y, Onoduka J, Homma KJ, Yamaguchi S, Mori M, Higashi Y, Makita M, Kinoshita T, Noda J, Itabe H, Takanoa T (2006) Long-chain fatty acids induce lipid droplet formation in a cultured human hepatocyte in a manner dependent of Acyl-CoA synthetase. Biol Pharm Bull 29:2174–2180CrossRefPubMedGoogle Scholar
- 19.Miura S, Gan JW, Brzostowski J, Parisi MJ, Schultz CJ, Londos C, Oliver B, Kimmel AR (2002) Functional conservation for lipid storage droplet association among perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium. J Biol Chem 277:32253–32257CrossRefPubMedGoogle Scholar
- 39.Waynforth HB, Fleccknell PA (1992) Experimental and surgical technique in the rat. Academic PressGoogle Scholar