Biogenesis of HDL by SAA is dependent on ABCA1 in the liver in vivo.
Serum amyloid A (SAA) was markedly increased in the plasma and in the liver upon acute inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS) in mice, and SAA in the plasma was exclusively associated with HDL. In contrast, no HDL was present in the plasma and only a small amount of SAA was found in the VLDL/LDL fraction (d < 1.063 g/ml) after the induction of inflammation in ABCA1-knockout (KO) mice, although SAA increased in the liver. Primary hepatocytes isolated from LPS-treated wild-type (WT) and ABCA1-KO mice both secreted SAA into the medium. SAA secreted from WT hepatocytes was associated with HDL, whereas SAA from ABCA1-KO hepatocytes was recovered in the fraction that was >1.21 g/ml. The behavior of apolipoprotein A-I (apoA-I) was the same as that of SAA in HDL biogenesis by WT and ABCA1-KO mouse hepatocytes. Lipid-free SAA and apoA-I both stabilized ABCA1 and caused cellular lipid release in WT mouse-derived fibroblasts, but not in ABCA1-KO mouse-derived fibroblasts, in vitro when added exogenously. We conclude that both SAA and apoA-I generate HDL largely in hepatocytes only in the presence of ABCA1, likely being secreted in a lipid-free form to interact with cellular ABCA1. In the absence of ABCA1, nonlipidated SAA is seemingly removed rapidly from the extracellular space.
Hu
Wei
W
Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Abe-Dohmae
Sumiko
S
Tsujita
Maki
M
Iwamoto
Noriyuki
N
Ogikubo
Osamu
O
Otsuka
Takanobu
T
Kumon
Yositaka
Y
Yokoyama
Shinji
S
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis; D041702:BALB 3T3 Cells; D016466:CHO Cells; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology; D008075:Lipoproteins, HDL / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D000685:Serum Amyloid A Protein / Q000502:physiology*
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein