PMID- 10634809
OWN - NLM
STAT- MEDLINE
DCOM- 20000128
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 20
IP  - 1
DP  - 2000 Jan
TI  - Induction of ubiquitin-conjugating enzyme by aggregated low density lipoprotein
      in human macrophages and its implications for atherosclerosis.
PG  - 128-34
AB  - Recently, we have found that aggregated low density lipoprotein (agLDL) inhibits 
      apoptosis of lipid-bearing macrophages, thereby facilitating foam cell formation 
      and atherosclerosis. To clarify the mechanisms by which agLDL inhibits apoptosis 
      of macrophages, we isolated the genes specifically induced by agLDL by using a
      subtraction-based cloning strategy. One of the cloned genes, termed low density
      lipoprotein (LDL)-inducible gene (LIG), encodes a human homologue of bovine
      ubiquitin-conjugating enzyme E2-25K. Although LIG mRNA was ubiquitously expressed
      among human tissues, including hematopoietic cells, the abundance of transcripts 
      was markedly increased by agLDL treatment in activated monocytes. LIG mRNA
      expression was not enhanced by nonatherogenic lipoproteins such as native LDL and
      high density lipoprotein, suggesting a role in atherosclerosis.
      Polyubiquitination of intracellular proteins was observed in monocytes cultured
      with agLDL, which coincided with upregulation of LIG. Furthermore,
      ubiquitin-dependent degradation of p53, an inducer of apoptosis, was accompanied 
      by LIG induction in agLDL-treated monocytes. The antiapoptotic effect of agLDL
      was abrogated by a specific proteasome inhibitor, which also increased the
      half-life of p53 in monocytes. These results suggest that LIG contributes to foam
      cell formation by the suppression of apoptosis of lipid-bearing macrophages
      through ubiquitination and subsequent degradation of p53.
FAU - Kikuchi, J
AU  - Kikuchi J
AD  - Division of Molecular Hemopoiesis, Center for Molecular Medicine, Jichi Medical
      School, Tochigi, Japan.
FAU - Furukawa, Y
AU  - Furukawa Y
FAU - Kubo, N
AU  - Kubo N
FAU - Tokura, A
AU  - Tokura A
FAU - Hayashi, N
AU  - Hayashi N
FAU - Nakamura, M
AU  - Nakamura M
FAU - Matsuda, M
AU  - Matsuda M
FAU - Sakurabayashi, I
AU  - Sakurabayashi I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (DNA, Complementary)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Ubiquitins)
RN  - EC 2.3.2.23 (UBE2K protein, human)
RN  - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis
MH  - Arteriosclerosis/*etiology/genetics/*metabolism
MH  - Base Sequence
MH  - Cattle
MH  - DNA, Complementary/genetics
MH  - Foam Cells/metabolism
MH  - Gene Expression
MH  - Humans
MH  - Kinetics
MH  - Ligases/*biosynthesis/genetics
MH  - Lipoproteins, LDL/*pharmacology
MH  - Macrophages/*drug effects/*metabolism
MH  - Molecular Sequence Data
MH  - Monocytes/drug effects/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - *Ubiquitin-Conjugating Enzymes
MH  - Ubiquitins/metabolism
EDAT- 2000/01/15 00:00
MHDA- 2000/01/15 00:01
CRDT- 2000/01/15 00:00
PHST- 2000/01/15 00:00 [pubmed]
PHST- 2000/01/15 00:01 [medline]
PHST- 2000/01/15 00:00 [entrez]
AID - 10.1161/01.atv.20.1.128 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):128-34. doi:
      10.1161/01.atv.20.1.128.