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Interaction Between Mevalonate Pathway and Retinoic Acid-Induced Differentiation.

Gueddari-Pouzols N, Duriez P, Chomienne C, Trussardi A, Jardillier JC - J. Biomed. Biotechnol. (2001)

Bottom Line: The supply of an excess of cholesterol (up to 80 &mgr;g/ml of LDL) leads to a significant decrease of cell differentiation by ATRA from 78% +/-0.1 to 54% +/-2.8.A concomitant decrease of cell growth (51% +/- 6.4) was observed.The pretreatment of cells by the geranylgeranyltransferase inhibitor (GGTI-298) has no effect on the cell differentiation process.

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ABSTRACT
All trans retinoic acid (ATRA) is a potent inducer of differentiation of HL-60 cell line. The pretreatment of the cells by compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, during 24 hours, enhances the ATRA-induced cell differentiation. At 50 nM, the percentage of cell differentiation is 34.9% +/- 2 and 73% +/- 2.96 in the control and compactin-treated cells, respectively. The removal of compactin boosts the level of HMG-CoA reductase and therefore the biosynthesis of sterol and nonsterol isoprenoid compounds. The participation of sterol and nonsterol pathway was then investigated. The supply of an excess of cholesterol (up to 80 &mgr;g/ml of LDL) leads to a significant decrease of cell differentiation by ATRA from 78% +/-0.1 to 54% +/-2.8. A concomitant decrease of cell growth (51% +/- 6.4) was observed. The pretreatment of cells by the geranylgeranyltransferase inhibitor (GGTI-298) has no effect on the cell differentiation process. By contrast, the farnesyltransferase inhibitors (FTI-II and FTI-277) completely abolish theATRA-induced differentiation, thus confirming the involvement of farnesylated proteins in the differentiation mechanism.

No MeSH data available.


Effect of higher low-density lipoprotein concentrations on growth and differentiation of HL-60 cells by ATRA. HL-60 cells were incubated during 5 days with 1 μM ATRA and increasing concentrations of LDL. Differentiation as determined by NBT reduction (∘) and viable cell number as determined by Trypan blue exclusion (▴).
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Figure 2: Effect of higher low-density lipoprotein concentrations on growth and differentiation of HL-60 cells by ATRA. HL-60 cells were incubated during 5 days with 1 μM ATRA and increasing concentrations of LDL. Differentiation as determined by NBT reduction (∘) and viable cell number as determined by Trypan blue exclusion (▴).

Mentions: In order to test the cholesterol effect on ATRA-induced cell differentiation, the cells were incubated in the presence of ATRA (1 μM) and increasing concentrations of LDL, up to 80 μg/ml. Under such conditions, the differentiation of ATRA-treated cells was decreased from 78% to 54% ± 2.8. Interestingly, a concomitant decrease of cell growth (48%) was evidenced in the presence of high concentrations of LDL (Figure 2).


Interaction Between Mevalonate Pathway and Retinoic Acid-Induced Differentiation.

Gueddari-Pouzols N, Duriez P, Chomienne C, Trussardi A, Jardillier JC - J. Biomed. Biotechnol. (2001)

Effect of higher low-density lipoprotein concentrations on growth and differentiation of HL-60 cells by ATRA. HL-60 cells were incubated during 5 days with 1 μM ATRA and increasing concentrations of LDL. Differentiation as determined by NBT reduction (∘) and viable cell number as determined by Trypan blue exclusion (▴).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC129055&req=5

Figure 2: Effect of higher low-density lipoprotein concentrations on growth and differentiation of HL-60 cells by ATRA. HL-60 cells were incubated during 5 days with 1 μM ATRA and increasing concentrations of LDL. Differentiation as determined by NBT reduction (∘) and viable cell number as determined by Trypan blue exclusion (▴).
Mentions: In order to test the cholesterol effect on ATRA-induced cell differentiation, the cells were incubated in the presence of ATRA (1 μM) and increasing concentrations of LDL, up to 80 μg/ml. Under such conditions, the differentiation of ATRA-treated cells was decreased from 78% to 54% ± 2.8. Interestingly, a concomitant decrease of cell growth (48%) was evidenced in the presence of high concentrations of LDL (Figure 2).

Bottom Line: The supply of an excess of cholesterol (up to 80 &mgr;g/ml of LDL) leads to a significant decrease of cell differentiation by ATRA from 78% +/-0.1 to 54% +/-2.8.A concomitant decrease of cell growth (51% +/- 6.4) was observed.The pretreatment of cells by the geranylgeranyltransferase inhibitor (GGTI-298) has no effect on the cell differentiation process.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
All trans retinoic acid (ATRA) is a potent inducer of differentiation of HL-60 cell line. The pretreatment of the cells by compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, during 24 hours, enhances the ATRA-induced cell differentiation. At 50 nM, the percentage of cell differentiation is 34.9% +/- 2 and 73% +/- 2.96 in the control and compactin-treated cells, respectively. The removal of compactin boosts the level of HMG-CoA reductase and therefore the biosynthesis of sterol and nonsterol isoprenoid compounds. The participation of sterol and nonsterol pathway was then investigated. The supply of an excess of cholesterol (up to 80 &mgr;g/ml of LDL) leads to a significant decrease of cell differentiation by ATRA from 78% +/-0.1 to 54% +/-2.8. A concomitant decrease of cell growth (51% +/- 6.4) was observed. The pretreatment of cells by the geranylgeranyltransferase inhibitor (GGTI-298) has no effect on the cell differentiation process. By contrast, the farnesyltransferase inhibitors (FTI-II and FTI-277) completely abolish theATRA-induced differentiation, thus confirming the involvement of farnesylated proteins in the differentiation mechanism.

No MeSH data available.