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R Sugano

Publications and source records attributed to R Sugano.

6 recordsLinked to original sources
PubMed2001

Uptake of oxidized low-density lipoprotein in a THP-1 cell line lacking scavenger receptor A.

We previously isolated THP-1 subtype cells (sTHP-1), a cell line that expresses scanty amounts of scavenger receptor A (ScR-A) and does not undergo foam cell formation when incubated with acetylated low-density lipoprotein (Ac-LDL). In this study, we investigated the accumulation of esterified cholesterol in sTHP-1 cells incubated with oxidized LDL (Ox-LDL), a physiologically modified lipoprotein in human. While sTHP-1 cells incubated with Ac-LDL accumulated only small amounts of esterified cholesterol, those incubated with Ox-LDL accumulated amounts similar to those accumulated by parent THP-1 (pTHP-1) cells. sTHP-1 cells expressed CD36 in amounts similar to the amounts expressed by pTHP-1 cells, and Ox-LDL was internalized through this CD36. The amount of accumulated esterified cholesterol was 73-81% of that accumulated in pTHP-1 cells expressing ScR-A. The levels of 125I-Ox-LDL binding, association, and degradation in sTHP-1 cells were 64-70% of the corresponding levels in pTHP-1 cells. In our experiments utilizing ScR-A-deficient sTHP-1 cells and a specific antibody against human CD36, most of the Ox-LDL interacted with the CD36 receptor. In addition, a substantial amount of Ox-LDL (28-42%) was bound and degraded by sTHP-1 macrophages when both of the two major scavenger receptors, ScR-A and CD36, were deficient or blocked. These results indicate that CD36 in macrophages plays an important role in foam cell formation by Ox-LDL, while additional scavenger receptor(s) may take part in significant pathways of Ox-LDL uptake in macrophages.

Blotting, Northern↗
PubMed1998

Acquisition of secretion of transforming growth factor-beta 1 leads to autonomous suppression of scavenger receptor activity in a monocyte-macrophage cell line, THP-1.

Macrophage cells derived from the human monocytic leukemia cell line, THP-1, accumulate esterified cholesterol when cultivated in the presence of acetylated low density lipoprotein (Ac-LDL) through scavenger receptors (ScR). In the present study, we isolated a subtype of THP-1 cells that failed to accumulate esterified cholesterol when cultivated in the presence of Ac-LDL. The cells had negligible amounts of cell association and degradation of Ac-LDL compared with the parent THP-1 cells. The subtype THP-1 cells did not express ScR mRNA as well as that of lipoprotein lipase. In contrast, the expression of apolipoprotein E mRNA was greater than that found in parent THP-1 cells. The culture medium of subtype THP-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate inhibited the uptake of Ac-LDL and the expression of ScR in parent THP-1 cells. After a 48-h incubation in the culture medium containing 12-O-tetradecanoylphorbol-13-acetate, the culture medium of differentiated subtype THP-1 cells contained 6.9 ng/ml transforming growth factor (TGF)-beta 1, while that of parent THP-1 cells secreted below detection level, which was less than 3 ng/ml. This inhibitory effect of the conditioned medium on the expression of ScR in parent THP-1 cells was abolished by pretreatment of the culture medium with anti-TGF-beta 1 antibodies. Parent THP-1 cells expressed as much TGF-beta 1 mRNA as sTHP-1 cells after stimulation of differentiation. Although the precursor forms of TGF-beta 1 that were synthesized in both parent and subtype THP-1 cells were of similar size and were expressed at similar levels, latent TGF-beta 1-binding protein, which is necessary for the secretion of TGF-beta 1, could only be co-immunoprecipitated with anti-TGF-beta 1 antibody from subtype THP-1 cells. This suggests that subtype THP-1 cells secrete TGF-beta 1 into the medium by forming a functional complex with the latent TGF-beta 1-binding protein. We conclude that subtype THP-1 cells could not take up Ac-LDL because ScR was inhibited (leading to a loss of function) caused by the secreted TGF-beta 1.

Carrier Proteins↗