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The PPARδ ligand GW501516 reduces growth but not apoptosis in mouse inner medullary collecting duct cells.

Clark J, Nasrallah R, Hébert RL - PPAR Res (2009)

Bottom Line: The collecting duct (CD) expresses considerable amounts of PPARδ.High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability.Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5.

ABSTRACT
The collecting duct (CD) expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth but does not affect anisomycin-apoptosis in a mouse IMCD cell line. This could have therapeutic implications for renal diseases associated with increased CD growth responses.

No MeSH data available.


Related in: MedlinePlus

PGE2 stimulates cAMP in IMCD-K2 cells.Serum-starved cells were stimulated for tenminutes with (a) 10−6 M of different prostanoids (cicaprost (CCP), iloprost (ILP), and PGE2)or 10−5 M forskolin (FOR), and with (b) differing concentrations of PGE2 (10−9 to 10−6 M). A competitive binding assay with 3H-cAMP wasperformed and the percent cAMP stimulation was determined using a scintillationcounter. Values are means  ±   S.E.M.; n = 3–4. *P < .05 compared to control.
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fig2: PGE2 stimulates cAMP in IMCD-K2 cells.Serum-starved cells were stimulated for tenminutes with (a) 10−6 M of different prostanoids (cicaprost (CCP), iloprost (ILP), and PGE2)or 10−5 M forskolin (FOR), and with (b) differing concentrations of PGE2 (10−9 to 10−6 M). A competitive binding assay with 3H-cAMP wasperformed and the percent cAMP stimulation was determined using a scintillationcounter. Values are means ± S.E.M.; n = 3–4. *P < .05 compared to control.

Mentions: Boththe EP3 and EP4 receptors elicit changes in intracellularcAMP; therefore, the effect of different prostanoids on cAMP stimulation wasexamined. Forskolin was used as a positive control. As shown in Figure 2(a), prostacyclin (PGI2) analogs cicaprost (CCP) andiloprost (ILP) did not alter cAMP levels. PGE2, however, did cause asignificant increase in percent stimulation, at about 70% above control,comparable to forskolin. As shown in Figure2(b), treatment with increasing amounts of PGE2 resulted in aconcentration-dependent increase in cAMP, from 14.0 to 85.5%.


The PPARδ ligand GW501516 reduces growth but not apoptosis in mouse inner medullary collecting duct cells.

Clark J, Nasrallah R, Hébert RL - PPAR Res (2009)

PGE2 stimulates cAMP in IMCD-K2 cells.Serum-starved cells were stimulated for tenminutes with (a) 10−6 M of different prostanoids (cicaprost (CCP), iloprost (ILP), and PGE2)or 10−5 M forskolin (FOR), and with (b) differing concentrations of PGE2 (10−9 to 10−6 M). A competitive binding assay with 3H-cAMP wasperformed and the percent cAMP stimulation was determined using a scintillationcounter. Values are means  ±   S.E.M.; n = 3–4. *P < .05 compared to control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2651001&req=5

fig2: PGE2 stimulates cAMP in IMCD-K2 cells.Serum-starved cells were stimulated for tenminutes with (a) 10−6 M of different prostanoids (cicaprost (CCP), iloprost (ILP), and PGE2)or 10−5 M forskolin (FOR), and with (b) differing concentrations of PGE2 (10−9 to 10−6 M). A competitive binding assay with 3H-cAMP wasperformed and the percent cAMP stimulation was determined using a scintillationcounter. Values are means ± S.E.M.; n = 3–4. *P < .05 compared to control.
Mentions: Boththe EP3 and EP4 receptors elicit changes in intracellularcAMP; therefore, the effect of different prostanoids on cAMP stimulation wasexamined. Forskolin was used as a positive control. As shown in Figure 2(a), prostacyclin (PGI2) analogs cicaprost (CCP) andiloprost (ILP) did not alter cAMP levels. PGE2, however, did cause asignificant increase in percent stimulation, at about 70% above control,comparable to forskolin. As shown in Figure2(b), treatment with increasing amounts of PGE2 resulted in aconcentration-dependent increase in cAMP, from 14.0 to 85.5%.

Bottom Line: The collecting duct (CD) expresses considerable amounts of PPARδ.High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability.Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5.

ABSTRACT
The collecting duct (CD) expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth but does not affect anisomycin-apoptosis in a mouse IMCD cell line. This could have therapeutic implications for renal diseases associated with increased CD growth responses.

No MeSH data available.


Related in: MedlinePlus