Hydrogen Peroxide Induces Upregulation of Fas in Human Airway Epithelial Cells via the Activation of PARP-p53 Pathway

Abstract

Fas mediates apoptosis following binding with Fas ligand. Fas is expressed in human airway epithelial cells and has a critical role in the pathophysiology of various pulmonary disorders. Hydrogen peroxide (H(2)O(2)) is an important mediator of airway epithelial injury. In this context, we hypothesized that H(2)O(2) would increase the expression of cell surface Fas in human airway epithelial cells. To test this hypothesis, the modulation of Fas expression with H(2)O(2) was assessed in normal human bronchial epithelial cells and A549 cells. The majority of Fas was cytoplasmic in both cell types without any stimulation. Hydrogen peroxide significantly increased Fas in the plasma membrane fraction, while decreasing Fas in the cytoplasmic fraction. Incubation with an agonistic antibody for Fas induced apoptosis in H(2)O(2)-treated cells in proportion to the level of surface Fas expression on those cells. Inhibitors of poly(ADP-ribose) polymerase abrogated the H(2)O(2)-induced Fas translocation to the plasma membrane and p53 activation. Expression of dominant-negative p53 also inhibited the Fas translocation induced by H(2)O(2) in A549 cells. These results indicate that H(2)O(2) induces Fas upregulation by promoting cytoplasmic transport of Fas to the cell surface in human airway epithelial cells, and that the activation of the poly(ADP-ribose) polymerase-p53 pathway may be involved in this mechanism.

The Antiproliferative Activity of Saponin-Enriched Fraction from Bupleurum Kaoi Is through Fas-Dependent Apoptotic Pathway in Human Non-small Cell Lung Cancer A549 Cells

“…22) Recent study has indicated that Fas/ APO-1 is expressed in human airway epithelial cells and has a critical role in the pathophysiology of various pulmonary disorders. 23) Upregulation of Fas/APO-1 expression has been demonstrated to induce apoptosis in hydrogen peroxidetreated A549 cells. Serrao et al have reported that neutrophils induce apoptosis of lung epithelial cells via release of soluble FasL.…”

Streptococcal Pyrogenic Exotoxin B-Induced Apoptosis in A549 Cells Is Mediated through α v β 3 Integrin and Fas

“…Fas is distributed mostly in cytoplasm and minimally on the cell surface in A549 cells in an unstimulated condition (13,31). In the presence of hydrogen peroxide, Fas was significantly increased on the plasma membrane and decreased in the cytoplasmic fraction (13), indicating that hydrogen peroxide increased the translocation of Fas from the cytosol to the plasma membrane. The expression of the Fas in A549 cells is also regulated by various external stimuli.…”

“…Apoptosis is critical in the development of acute lung injury, during which the Fas and Fas ligand pathway is activated (28). Fas is distributed mostly in cytoplasm and minimally on the cell surface in A549 cells in an unstimulated condition (13,31). In the presence of hydrogen peroxide, Fas was significantly increased on the plasma membrane and decreased in the cytoplasmic fraction (13), indicating that hydrogen peroxide increased the translocation of Fas from the cytosol to the plasma membrane.…”

SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice

“…Apoptosis of A549 cells, a lung epithelial cell line, was reported to be induced by ionizing radiation and treatment with an agonistic Fas antibody [27,28]. Here, we assessed the role of SRT1720 on apoptosis in A549 cells.…”