Proapoptotic effects of parathyroid hormone-related protein in type II pneumocytes.
Proapoptotic effects of parathyroid hormone-related protein in type II pneumocytes.
复制标题
甲状旁腺激素相关蛋白对 II 型肺细胞的促凋亡作用。
DOI：
10.1165/rcmb.2002-0314oc
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Deftos,LeonardJ
中科院分区：
文献类型：
--
作者：
Hastings,RandolphH;Quintana,RickA;Sandoval,Rebeca;Duey,Devin;Rascon,Yvette;Burton,DouglasW;Deftos,LeonardJ
Parathyroid hormone–related protein (PTHrP) promotes or suppresses apoptosis in various settings depending on cell type and context. PTHrP 1–34 and PTHrP 67–86 are type II cell growth factors with effects on pneumocyte growth and surfactant secretion. This study investigated the effects of 24 h pretreatment with these two peptides on rat type II cell apoptosis after 0.3 J/cm2ultraviolet-B irradiation. Adherent cells decreased in number by 15 ± 5% and nonadherent cells increased > 5-fold 24 h after ultraviolet irradiation. Cell loss was due predominantly to apoptosis, based on ethidium bromide exclusion, nuclear condensation, and caspase 3 activity. Nuclear condensation increased from 15.6 ± 2.2% of irradiated cells with no treatment to 25.6 ± 4.9 and 22.9 ± 1.8% of cells in ultraviolet/PTHrP 1–34 and ultraviolet/PTHrP 67–86 groups, respectively (P< 0.01), along with a 60% increase in caspase 3 activity. Effects on apoptosis were unaffected by the presence or absence of serum, but were ameliorated by growth to confluence or adherence to fibronectin. PTHrP 1–34 and PTHrP 67–86 augmented inositol phosphate levels, but had minimal effects on cAMP. Thus, PTHrP 1–34 and PTHrP 67–86 sensitize type II cells to apoptosis, possibly by a phospholipase C–dependent mechanism. The effects appear to be regulated by cell–matrix and cell–cell interactions.
