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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1989-3-27
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pubmed:abstractText |
Transcription of the low density lipoprotein receptor (LDL-R) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase genes was rapidly and transiently induced (8.5- and 2.3-fold, respectively) early during phorbol 12-myristate 13-acetate (PMA)-induced macrophage differentiation of the human monocytic leukemia cell line THP-1. The levels of mRNA coding for LDL-R and HMG-CoA reductase increased soon after induction, reached a maximum (12- and 7-fold increase, respectively) in 2-3 hr, and then rapidly returned to the low constitutive levels observed before induction. The stability of LDL-R mRNA did not change significantly during differentiation, whereas that of HMG-CoA reductase mRNA decreased by about 5-fold 6 hr after the addition of PMA. Transcriptional induction of both LDL-R and HMG-CoA reductase genes (5.6- and 2-fold, respectively) was also observed when undifferentiated cells were treated with cycloheximide (CHX), resulting in a transient increase in steady-state mRNA (7- and 3-fold, respectively). These results suggest that expression of the two genes is maintained at low constitutive levels in uninduced THP-1 cells by a protein with a short half-life. Superinduction of both genes occurred when PMA and CHX were added simultaneously. The induction of LDL-R and HMG-CoA reductase mRNAs during early macrophage differentiation is mediated by protein kinase C. It is hypothesized that protein kinase C acts directly or indirectly to inactivate the labile negative regulatory protein. Induction of LDL-R mRNA was also observed when the human hepatocarcinoma cell line Hep G2 was treated with PMA and CHX, suggesting that this mechanism of regulation may exist in several cell types.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-212203,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-229107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-2431274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-2443796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-2991281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3014651,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3030558,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3030751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3034433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3037355,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3140380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3277969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3401441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3476117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3600629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3708688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3855620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3860301,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3881183,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-3932352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6091915,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6143315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6239622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6271886,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6311077,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6397553,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6577438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6583685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6863296,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6893015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6949641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2919164-6961444
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
86
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1133-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:2919164-Cell Line,
pubmed-meshheading:2919164-Genes,
pubmed-meshheading:2919164-Genes, Regulator,
pubmed-meshheading:2919164-Humans,
pubmed-meshheading:2919164-Hydroxymethylglutaryl CoA Reductases,
pubmed-meshheading:2919164-Kinetics,
pubmed-meshheading:2919164-Protein Kinase C,
pubmed-meshheading:2919164-RNA, Messenger,
pubmed-meshheading:2919164-Receptors, LDL,
pubmed-meshheading:2919164-Tetradecanoylphorbol Acetate,
pubmed-meshheading:2919164-Transcription, Genetic
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pubmed:year |
1989
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pubmed:articleTitle |
Regulation of the low density lipoprotein receptor and hydroxymethylglutaryl coenzyme A reductase genes by protein kinase C and a putative negative regulatory protein.
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pubmed:affiliation |
Department of Medicine, University of Washington, Seattle 98195.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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