Anti-apoptotic PTD–FNK protein suppresses lipopolysaccharide-induced acute lung injury in rats
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- 作者：He Chen ; Lei Zhang ; Zhanfeng Jin ; Enjing Jin ; Masakazu Fujiwara ; Mohammad Ghazizadeh ; Sadamitsu Asoh ; Shigeo Ohta ; Oichi Kawanami
- 关键词：PTD– ; FNK protein ; Anti-apoptosis ; Acute lung injury ; Lipopolysaccharide ; Rat model
- 刊名：Experimental and Molecular Pathology
- 出版年：2007
- 出版时间：December 2007
- 年：2007
- 卷：83
- 期：3
- 页码：377-384
- 全文大小：1273 K
文摘
The present study was aimed at clarifying the effects of an anti-apoptotic protein for modulating symptoms in acute lung injury (ALI). From Bcl-xL, a Bcl-2 family member, we constructed an artificial protein (FNK) and fused it with the protein transduction domain (PTD) of the HIV/Tat protein (PTD–FNK) to facilitate its permeation into cells. ALI was induced by intratracheal infusion of lipopolysaccharide (LPS) into Sprague–Dawley male rats. PTD–FNK was injected into the peritoneal cavity of the animals either 2 h before, or 3 h or 6 h after LPS challenge. All rats were sacrificed 24 h after the last treatment. Cell differential ratios and albumin concentration were estimated in bronchoalveolar lavage fluid. We examined histological change, myeloperoxidase activity, TUNEL assay, caspase-3/caspase-3-like activity and immunohistochemical reaction for caspase 3 (active form). In animals with PTD–FNK treatment, the albumin leakage was significantly attenuated with protection of tissue damage. Also, the apoptosis of alveolar wall cells was reduced by PTD–FNK treatment, while a total cell number and the neutrophil ratio were not changed. Human umbilical vein endothelial cells (HUVEC) and cells of an alveolar epithelial cell line (A549) were exposed to LPS or TNF-α with or without PTD–FNK treatment in vitro. Cell survival rates examined by trypan-blue exclusion assay were increased by PTD–FNK treatment in a concentration-dependent manner. Thus, PTD–FNK could play a protective role in ALI by suppressing apoptosis of alveolar epithelial cells and capillary endothelial cells despite of some effect on neutrophil activity.