Schulte E A, Saleh H, Schlatter E
Westfälische Wilhelms-Universität, Medizinische Poliklinik, Experimentelle Nephrologie, Münster, Deutschland.
Cell Physiol Biochem. 2000;10(1-2):57-64. doi: 10.1159/000016334.
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.
血管活性激素和生长因子对细胞增殖的调节还涉及pH调节转运蛋白活性的变化。在之前的一篇论文中(1)，我们研究了这些因素对细胞pH值的影响。在此，通过对[3H] - 胸腺嘧啶核苷掺入量的定量分析，研究了相同因素，即多磷酸二腺苷(ApnA)、心房利钠肽、生长因子血小板衍生生长因子(PDGF)和Ca2 + - ATP酶抑制剂毒胡萝卜素，对培养的大鼠系膜细胞增殖的影响。在实验开始前，将系膜细胞同步化并降低生长速度(0.5%胎牛血清处理24小时)。用Ap3A、Ap4A、Ap5A或Ap6A(均为10微摩尔)孵育24小时，均使细胞增殖降低30%至45%。在0.1微摩尔和1微摩尔浓度下，Ap4A、Ap5A和Ap6A的作用不显著。当细胞孵育24、48或72小时时，Ap5A的抗有丝分裂作用无显著差异。此外，Ap5A对第二代、第六代或第十三代细胞的抗增殖作用也无显著差异。生长因子PDGF - BB(0.25纳摩尔)使[3H] - 胸腺嘧啶核苷掺入量增加约3倍。与10微摩尔Ap5A共同孵育可显著降低这种增殖增加。在Ca2 + - ATP酶抑制剂毒胡萝卜素(1纳摩尔)存在的情况下，PDGF的促有丝分裂作用完全被消除，毒胡萝卜素还使基础细胞增殖显著降低约40%。用10纳摩尔心房利钠肽孵育系膜细胞24小时，使基础[3H] - 胸腺嘧啶核苷掺入量略有降低约20%，并减弱了PDGF诱导的刺激作用。当细胞受到刺激时，这些激动剂的抗有丝分裂作用尤为明显。
