P21, Bax and Caspase-3 participate in the propagating mechanism of apoptosis in the human gastric epithelial cells

Abstract

Background and Aims: Apoptosis can be defined as the cell death programmed inherently. Bcl-2 family proteins such as Bcl-2, Bax and Bak act as preventive or promotive factors for apoptosis. Caspases are located in the common pathway to apoptosis, and act as the executors of apoptosis. Apoptosis is also closely related to the cell cycle, so that p21, a cyclin dependent kinase inhibitor, is also implicated in apoptotic process. In the human gastric mucosa, it is known that apoptotic cell death is upregulated relating to Helicobacter pylori (HP) infection, and the disintegration of apoptotic system, which excludes damaged cells may lead to carcinogenesis. However, it is unclear how apoptotic signals propagate in the human gastric mucosa.Therefore, we studied the apoptotic pathway in the human gastric mucosa. Materials and Methods: Gastric mucosal specimens were obtained from 10 HP-negative dyspepsia patients, 10 HP-positive chronic gastritis patients before and after HP eradication. Immunohistochemistry of Ki-67, p21, Caspase-3, Bax and Bak was performed and apoptotic cells were detected by the TUNEL method. Results: Ki-67 immunoreactivity was identified in the nuclei of proliferative cells located in the mucosal neck region, and the number of Ki-67 positive cells increased in HP positive gastric mucosa. Immunoreactivity of p21 was detected in the nuclei of the cells located in the area of more luminal than the cell proliferation area toward the mucosal surface. Immunoreactivities of caspase-3 and Bax increased in the cytoplasm and nuclei of the cells that were located predominantly in the upper part of surface mucosa. Bak did not show any remarkable changes. TUNEL positive cells were predominantly found at the tip of mucosa. The cells positive for p21 were also sporadically observed in the gastric gland, but they did not coincided with the caspase-3or Bax-positive cells. The expression of all these molecules was increased in the HP positive gastric mucosa and was decreased after HP eradication. Conclusions: The present data suggested that apoptotic signal may propagate in the gastric surface epithelium through the upregulation of p21, Bax and caspase-3 in both the normal and inflamed gastric surface mucosa, which would be set in just after cell proliferation. On the other hand, apoptosis in the gastric glandular cells might be regulated by different mechanisms from the surface epithelium.