Overexpression of SND p102, a rat homologue of p100 coactivator, promotes the secretion of lipoprotein phospholipids in primary hepatocytes.
SND p102 belongs to an evolutionarily conserved family of proteins first described as transcriptional coactivators, whose biological function has not yet been defined. High expression levels of homologues of SND p102 in non-nuclear compartments of lipid secretory tissues and in murine liver endoplasmic reticulum suggest a role for SND p102 in lipoprotein secretion in hepatocytes. To address this issue, after ascribing by confocal microscopy and Western blotting a non-nuclear localization of SND p102 in rat hepatocytes, we cloned its full-length cDNA, developed adenoviral vectors encoding the cDNA or a specific antisense sequence, and characterized the lipoprotein particles created and released for 24 h by transfected rat hepatocytes. The cellular ability to secrete apoB and apoA-I was not affected by SND p102 differential expression, nor was that of lipoproteins-triglyceride, -cholesterol and -cholesteryl esters. However, cells overexpressing SND p102 secreted phospholipid-rich lipoproteins. Compared with hepatocytes with basal or attenuated SND p102 expression, they secreted approximately 45% and 80% more phospholipid in d<1.015 g/mL and 1.015<d<1.24 g/mL lipoproteins, respectively. Oversecretion affected all phospholipid classes and did not significantly disturb the cellular phospholipid homeostasis. Collectively, the results suggest a specific, positive association of SND p102 and phospholipid release in lipoprotein particles in hepatocytes.
Palacios
Lourdes
L
Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country, Sarriena s/n, 48940 Leioa, Spain.
Ochoa
Begoña
B
Gómez-Lechón
María José
MJ
Castell
José Vicente
JV
Fresnedo
Olatz
O
D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004720:Endonucleases; D005260:Female; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics
D018076:DNA, Complementary; D008079:Lipoproteins, VLDL; D009687:Nuclear Proteins; D010743:Phospholipids; D015534:Trans-Activators; D004720:Endonucleases; C095221:SND1 protein, human; C490639:Snd1 protein, rat