Abstract: Alginate oligosaccharides were prepared by hydrolyzing alginate with algae lyase from Isoptericola halotolerans CGMCC 5336. The components were analyzed by liquid chromatography-mass spectrometry and purified by gel chromatography. Four main components, named Fr1, Fr2, Fr3, and Fr4, were purified and identified. Their effects on the transcription and translation of low-density-lipoprotein receptor (LDLR) gene and pro-protein convertase subtilisin/kexin type 9 (PCSK9) were investigated. The results showed that Fr1 contained two oligosaccharides, pento- and hexo-oligosaccharides; Fr2, Fr3 and Fr4 were tetra-, tri- and di-oligosaccharides. Among them, Fr1, Fr3, and Fr4 significantly up-regulated the level of LDLR while Fr3 down-regulated the level of PCSK9, indicating that the up-regulated LDLR by Fr3 might be related to PCSK9. The up-regulation of LDLR by Fr4 was not related to PCSK9, however, might be regulated by the sterol response binding protein-2 (SREBP-2). These indicated that Fr3 and Fr4 may be further developed as new food additives for lowering the plasma cholesterol level.
 BROWN M S, GOLDSTEIN J L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor[J]. Cell, 1997, 89(3): 331-340.<br />
 BROWN M S, GOLDSTEIN J L, BROWN M S, et al. Lipoprotein receptors in the liver. Control signals for plasma cholesterol traffic[J]. Journal of Clinical Investigation, 1983, 72(3): 743-747.<br />
 TAVORI H, RASHID S, FAZIO S. On the function and homeostasis of PCSK9: reciprocal interaction with LDLR and additional lipid effects[J]. Atherosclerosis, 2015, 238(2): 264-270.<br />
 MAXWELL K N, FISHER E A, BRESLOW J L. Over of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment[J]. Proceedings of the National Academy of Sciences of the United States of America, 2005, 102(6): 2 069-2 074.<br />
 SEIDAH N G, BENJANNET S, WICKHAM L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation[J]. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(3): 928-933.<br />
 LANGHI C, LE-MAY, GMYR V, et al. PCSK9 is expressed in pancreatic delta-cells and does not alter insulin secretion[J]. Biochemical & Biophysical Research Communications, 2009, 390(4): 1 288-1 293.<br />
 FERRI N, TIBOLLA G, PIRILLO A, et al. Proprotein convertase subtilisin kexin type 9 (PCSK9) secreted by cultured smooth muscle cells reduces macrophages LDLR levels[J]. Atherosclerosis, 2012, 220(2): 381-386<br />
 ZHANG D W, LAGACE T A, GARUTI R, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation[J]. Journal of Biological Chemistry, 2007, 282(25): 18 602-18 612.<br />
 HORTON J D, COHEN J C, HOBBS H H. PCSK9: a convertase that coordinates LDL catabolism[J]. Journal of Lipid Research, 2009, 50 (Supplement): S172-S177.<br />
 VREELAND V. Immunocytochemical localization of the extracellular polysaccharide alginic acid in the brown seaweed, Fucus distichus[J]. The Journal of Histochemistry and Cytochemistry,1972, 20(5): 358-367.<br />
 HAUG A, LARSEN B, SMIDSR D O, et al. A study of the constitution of alginic acid by partial acid hydrolysis[J]. Acta Chemica Scandinavica, 1966, 20: 183-190.<br />
 HAUG A, LARSEN B, SMIDSR D O, et al. Studies on the sequence of uronic acid residues in alginic acid[J]. Acta Chemica Scandinavica, 1967, 21: 691-704.<br />
 YANG J H, BANG M A, JANG C H, et al. Alginate oligosaccharide enhances LDL uptake via regulation of LDLR and PCSK9 [J]. Journal of Nutritional Biochemistry, 2015, 26(11):1 393-1 400.