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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

GW501516 causes a decrease in DNAsynthesis at high doses. Serum-starvedcells were stimulated for 24 hours with serum-free media (control) orincreasing concentrations of GW501516 (10−8 to 10−5 M) 3H-thymidinewas added to IMCD-K2 cells while they were being stimulated and thymidineincorporation was measured in counts per minute using a scintillation counter,and expressed as fold control. Values are mean  ±   S.E.M.; n = 3. *P < .05 compared to control.
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fig5: GW501516 causes a decrease in DNAsynthesis at high doses. Serum-starvedcells were stimulated for 24 hours with serum-free media (control) orincreasing concentrations of GW501516 (10−8 to 10−5 M) 3H-thymidinewas added to IMCD-K2 cells while they were being stimulated and thymidineincorporation was measured in counts per minute using a scintillation counter,and expressed as fold control. Values are mean ± S.E.M.; n = 3. *P < .05 compared to control.

Mentions: PPARδ has been known to affect cell proliferation;therefore, we studied the effect of the PPARδ agonist, GW501515, on the proliferation/growthof IMCD-K2 cells. As shown in Figure 5, 10−5 M GW501516 reduced 3H-thymidineincorporation to about 0.05-fold control. PPARδ also regulates cell growth and as shown in Figure6, 10−5 M GW501516 produced a significant reduction in 3H-leucineincorporation to approximately 0.19 of control. At lower concentrations ofGW501516, neither DNA nor protein synthesis was altered.


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)

GW501516 causes a decrease in DNAsynthesis at high doses. Serum-starvedcells were stimulated for 24 hours with serum-free media (control) orincreasing concentrations of GW501516 (10−8 to 10−5 M) 3H-thymidinewas added to IMCD-K2 cells while they were being stimulated and thymidineincorporation was measured in counts per minute using a scintillation counter,and expressed as fold control. Values are mean  ±   S.E.M.; n = 3. *P < .05 compared to control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: GW501516 causes a decrease in DNAsynthesis at high doses. Serum-starvedcells were stimulated for 24 hours with serum-free media (control) orincreasing concentrations of GW501516 (10−8 to 10−5 M) 3H-thymidinewas added to IMCD-K2 cells while they were being stimulated and thymidineincorporation was measured in counts per minute using a scintillation counter,and expressed as fold control. Values are mean ± S.E.M.; n = 3. *P < .05 compared to control.
Mentions: PPARδ has been known to affect cell proliferation;therefore, we studied the effect of the PPARδ agonist, GW501515, on the proliferation/growthof IMCD-K2 cells. As shown in Figure 5, 10−5 M GW501516 reduced 3H-thymidineincorporation to about 0.05-fold control. PPARδ also regulates cell growth and as shown in Figure6, 10−5 M GW501516 produced a significant reduction in 3H-leucineincorporation to approximately 0.19 of control. At lower concentrations ofGW501516, neither DNA nor protein synthesis was altered.

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