Document Detail

Stimulation of the proliferation of the Madin-Darby canine kidney (MDCK) epithelial cell line by high-density lipoproteins and their induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.
MedLine Citation:
PMID:  6352714     Owner:  NLM     Status:  MEDLINE    
MDCK Cells seeded on extracellular matrix- (ECM) coated dishes and exposed to medium supplemented with high-density lipoproteins (HDLs, 750 micrograms protein/ml) and transferrin (10 micrograms/ml) have a proliferative rate, final cell density, and morphological appearance similar to those of cells grown in serum-supplemented medium. The mitogenic stimulus provided by HDLs is not limited by the initial cell density at which cultures are seeded, nor is it limited in time, since cells grown in medium supplemented with transferrin and HDLs grew to at least 50 generations. The presence of HDLs in the medium is required in order for cells to survive, since cells actively proliferating in the presence of medium supplemented with HDLs and transferrin begin to die within 2 days after being transferred to medium supplemented only with transferrin. Low-density lipoprotein (LDL) is mitogenic for MDCK cells when present at low concentrations (from 2.5 to 100 micrograms protein/ml). Above 100 micrograms protein/ml, LDL is cytotoxic and therefore cannot support cell proliferation at an optimal rate. The mitogenic effect of HDLs is also observed when cells are maintained on fibronectin-coated dishes. However, the proliferative rate of the cells is suboptimal and cultures cannot be passaged on this substrate indefinitely, as they can be on ECM-coated dishes. A close association between the ability of HDLs to support cell proliferation and their ability to induce the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is observed. HMG CoA reductase activity is 18 times higher (70 pmoles/min/10(6) cells) in proliferating cells than in confluent, nondividing cells (4 pmoles/min/10(6) cells). The HMG Coa reductase activity of sparse cells is more sensitive to induction by HDLs (eight-fold higher than control cells) than is the enzyme activity of confluent cells (two-fold higher than control levels). The dose-response relationship between the abilities of HDLs to support proliferation and to induce HMG CoA reductase activity are similar. The time course of the stimulation of proliferation and the increase in enzyme activity of sparse, quiescent cells after exposure to HDLs are parallel. The HMG CoA reductase activity of sparse MDCK cells is induced six-fold by exposure to compactin, a competitive inhibitor of HMG CoA reductase. This induction of HMG CoA reductase is prevented by mevalonic acid, not affected by LDL, and synergistically enhanced by simultaneous exposure to HDLs. HDLs effect a rescue from the cytotoxic effect of compactin, whereas LDL does not.(ABSTRACT TRUNCATED AT 400 WORDS)
D Gospodarowicz; D C Cohen; S L Massoglia
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  117     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1983 Oct 
Date Detail:
Created Date:  1983-11-23     Completed Date:  1983-11-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  76-90     Citation Subset:  IM    
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MeSH Terms
Cell Division*
Cell Line
Cell Survival / drug effects
Enzyme Induction
Extracellular Matrix / physiology
Hydroxymethylglutaryl CoA Reductases / metabolism*
Insulin / physiology
Lipoproteins, HDL / physiology*
Lipoproteins, LDL / physiology
Lovastatin* / analogs & derivatives*
Naphthalenes / pharmacology
Transferrin / pharmacology
Grant Support
Reg. No./Substance:
0/Lipoproteins, HDL; 0/Lipoproteins, LDL; 0/Naphthalenes; 11061-68-0/Insulin; 11096-37-0/Transferrin; 73573-88-3/compactin; 75330-75-5/Lovastatin; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases

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