Relationship of ornithine decarboxylase activity and cAMP metabolism to proliferation of normal human bronchial epithelial cells

Relationship of ornithine decarboxylase activity and cAMP metabolism to proliferation of normal human bronchial epithelial cells
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鸟氨酸脱羧酶活性及cAMP代谢与正常人支气管上皮细胞增殖的关系

DOI:
10.1002/jcp.1041240206
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发表时间:
1985
影响因子:
5.6
通讯作者:
J. Lechner
J. Lechner
中科院分区:
生物学2区
文献类型:
--
作者:
J. Willey;M. A. Laveck;I. McClendon;J. Lechner

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通过观察细胞在无血清培养基中孵育时对选定生化途径的影响,研究了细胞外有丝分裂原对正常人支气管上皮细胞(NHBE)的作用机制。我们发现:(a)表皮生长因子(EGF)刺激鸟氨酸脱羧酶(ODC)活性和细胞分裂速率,而不刺激cAMP;(B)单独使用垂体提取物(PEX)不刺激ODC活性、cAMP水平或细胞分裂;(c)当将PEX加入到含有EGF的培养基中时,ODC活性和细胞分裂速率都进一步增加,同样,cAMP水平没有增加;(d)相反,单独的L-肾上腺素(EPI)刺激ODC和cAMP两者的增加,但不刺激细胞分裂;(e)当将EPi添加到含有EGF和PEX两者的培养基中时,注意到细胞分裂速率的进一步增加;(f)ODC的特异性抑制剂α-(二氟甲基)-鸟氨酸(DMFO)也抑制NHBE细胞增殖;和(g)β-肾上腺素能受体拮抗剂普萘洛尔抑制在条件e下观察到的EPI的促有丝分裂作用和ODC诱导。我们的结论是ODC活性的增加是必要的,但不足以增加NHBE细胞的增殖。相反,cAMP刺激对于NHBE细胞分裂的增加不是必需的。然而,在PEX中存在不确定因素的情况下,cAMP水平的增加导致EGF刺激的克隆生长速率的协同增加。通过将EGF、PEX、EPI及其组合所引起的生化途径与它们的促有丝分裂作用相关联,我们更好地定义了这些不同的促有丝分裂剂中的每一种在刺激上皮细胞分裂中所起的作用。
The mechanisms of action of extracellular mitogens for normal human bronchial epithelial cells (NHBE) were investigated by observing their effects on selected biochemical pathways when the cells were incubated in serum‐free media. We find that (a) epidermal growth factor (EGF) stimulates ornithine decarboxylase (ODC) activity and the rate of cell division without stimulating cAMP; (b) alone, pituitary extract (PEX) does not stimulate ODC activity, cAMP levels, or cell division; (c) when PEX is added to medium containing EGF there is a further increase in both ODC activity and the rate of cell division, again with no increase in cAMP levels; (d) in contrast, alone, L‐epinephrine (EPI) stimulates an increase in both ODC and cAMP but does not stimulate cell division; (e) when EPi is added to medium containing both EGF and PEX a further increase in the rate of cell division is noted; (f) the specific inhibitor of ODC, α‐ (difluoromethyl)‐ornithine (DMFO), also inhibits NHBE cell proliferation; and (g) the β‐adrenergic receptor antagonist propranolol inhibits the mitogenic action and ODC induction by EPI observed under condition e. We conclude that an increase in ODC activity is necessary but not sufficient for an increase in proliferation of NHBE cells. In contrast, cAMP stimulation is not necessary for an increase in NHBE cell division. However, in the presence of undefined factors in PEX, increases in cAMP levels result in a synergistic increase in the rate of EGF‐stimulated clonal growth. By correlating the biochemical pathways invoked by EGF, PEX, EPI, and combinations thereof with their mitogenic actions, we have better defined the role each of these different mitogens plays in stimulating epithelial cell division.
来自多头绒泡菌的细胞核和核仁的多胺激活蛋白激酶反应,磷酸化独特的 Mr 70 000 非组蛋白。
DOI: 10.1021/bi00512a025
发表时间: 1981
期刊: Biochemistry
影响因子: 2.9
作者:
Daniels,GR;Atmar,VJ;Kuehn,GD
通讯作者: Kuehn,GD