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Diadenosine polyphosphates and atrial natriuretic peptide are antiproliferative in rat mesangial cells
E A Schulte1, H Saleh, E Schlatter
1Westfälische Wilhelms-Universität, Medizinische Poliklinik, Experimentelle Nephrologie, Münster, Deutschland.
Abstract:
Modulation of cell proliferation by vasoactive hormones and growth factors involves also changes in the activity of pH-regulatory transporters. In a preceeding paper (1) we examined the influence of such factors on cellular pH Here the influence of the same factors, diadenosine polyphosphates (ApnA), atrial natriuretic peptide, the growth factor PDGF and the Ca2+-ATPase inhibitor thapsigargin, on proliferation of cultured rat mesangial cells was examined by quantification of [3H]-thymidine incorporation. Mesangial cells were synchronised and growth reduced (0.5% FCS for 24 h) before experiments were started, Incubation with Ap3A, Ap4A, Ap5A or Ap6A (all 10 microM) for 24 h all reduced cell proliferation by 30 to 45%. At 0.1 and 1 microM the effects of Ap4A, Ap5A and Ap6A did not reach significance The antimitogenic effect of Ap5A was not significantly different when cells were incubated for 24, 48 or 72 h. In addition there was no significant difference between the antiproliferative effect of Ap5A in cells of the second, sixth or thirteenth passage. The growth factor PDGF-BB (0.25 nM) resulted man approximately 3-fold increase in [3H]-thymidine incorporation. This increase in proliferation could be significantly reduced by coincubation with 10 microM Ap5A. The mitogenic effect of PDGF was completely abolished in the presence of the Ca2-ATPase inhibitor thapsigargin (1 nM), which also significantly reduced basal cell proliferation by approximately 40%. Incubation of mesangial cells with 10 nM ANP for 24 h reduced basal [3H]-thymidine incorporation slightly by approximately 20% and decreased the PDGF-induced stimulation. The antimitogenic effects of these agonists is especially pronounced when cells are stimulated.
Insights
Diadenosine polyphosphates (ApnA) and atrial natriuretic peptide inhibit rat mesangial cell proliferation. These compounds, along with PDGF and thapsigargin, affect cell growth, with Ap5A showing significant antiproliferative effects.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Cell proliferation is modulated by vasoactive hormones and growth factors.
- pH-regulatory transporters play a role in these modulations.
- Previous work examined the influence of these factors on cellular pH.
Purpose of the Study:
- To investigate the influence of diadenosine polyphosphates (ApnA), atrial natriuretic peptide (ANP), platelet-derived growth factor (PDGF), and thapsigargin on cultured rat mesangial cell proliferation.
- To quantify the effects of these agents on [3H]-thymidine incorporation.
Main Methods:
- Rat mesangial cells were synchronized and growth-restricted.
- Cells were incubated with various concentrations of ApnA, ANP, PDGF-BB, and thapsigargin.
- [3H]-thymidine incorporation was quantified to measure cell proliferation.
Main Results:
- Ap3A, Ap4A, Ap5A, and Ap6A (10 microM) reduced cell proliferation by 30-45%.
- Ap5A demonstrated a consistent antimitogenic effect across different incubation times and cell passages.
- PDGF-BB increased proliferation threefold, an effect reduced by Ap5A and abolished by thapsigargin.
- ANP slightly reduced basal proliferation and PDGF-induced stimulation.
Conclusions:
- Diadenosine polyphosphates and ANP exhibit antiproliferative effects on rat mesangial cells.
- Thapsigargin significantly inhibits both basal and PDGF-induced proliferation.
- These findings highlight the complex interplay between signaling molecules and cell proliferation regulation.