X irradiation induced colonic mucosal injury and the detection of apoptosis through PARP-1/p53 regulatory pathway

Free radicals due to irradiation causes lipid peroxidation in the structure of cell membranes of the Lieberkuhn cripts. After the destruction of cell membrane cytochrome c is oscillated from the mitochondrial inner membrane to the cytoplasm and activates apoptosis pathway. Caspase 9 and afterwards c...

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Veröffentlicht in:Biomedicine & pharmacotherapy 2020-07, Vol.127, p.110134-110134, Article 110134
Hauptverfasser: Akpolat, Meryem, Oz, Zehra Safi, Gulle, Kanat, Hamamcioglu, Ayse C., Bakkal, Bekir H., Kececi, Mete
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Sprache:eng
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Zusammenfassung:Free radicals due to irradiation causes lipid peroxidation in the structure of cell membranes of the Lieberkuhn cripts. After the destruction of cell membrane cytochrome c is oscillated from the mitochondrial inner membrane to the cytoplasm and activates apoptosis pathway. Caspase 9 and afterwards caspase 3 expression increases. Caspase 3 attaches the related part of PARP-1 and cleavage off this part and inactivated PARP-1 can not repair DNA damage which then causes apoptosis of the cell. In addition to this, the breakage of DNA structure due to irradiation activates p53 and stimulates apoptosis via the caspase cascade. [Display omitted] •This study aimed to investigate the roles of caspase 3, p53 and PARP-1 within the Lieberkühn crypts, following whole-body X-irradiation.•The enhancement of PARP-1, caspase 3 and p53 expressions was especially found in Lieberkühn crypts 6 h after irradiation.•In our study, 6 h after irradiation, the increase in both apoptosis and p53 expression demonstrated that p53 affects the relationship between PARP-1 and caspase 3. This study aimed to explore whether PARP-1 regulatory pathway mediated X irradiation induced cell cycle arrest and apoptosis or not. In this regard, colonic mucosal injury caused by whole-body X-irradiation induced apoptosis through PARP-1, caspase 3 and p53 regulatory pathway were evaluated in experimental rat models. Eighteen Wistar albino rats were divided into three groups. Two radiation groups received 8.3 Gy dose of whole-body X-irradiation as a single dose and the control group received physiological saline intraperitoneally. Radiation groups were sacrificed after 6 h and 4 days of irradiation. PARP-1 and caspase 3 expression in the nuclei of colonic crypt cells significantly increased 6 h after irradiation, and declined 4 days after irradiation. In conflict with other studies that reported p53 as not being expressed widely in colonic mucosa, in our study the expressions of p53 were elevated both in the cytoplasm and in the nucleus of the crypt cells, especially 6 h after irradiation. In the radiation groups, colonic mucosal injury score was significantly elevated compared with that of the control group. Our data demonstrated that PARP-1, caspase-3 and p53 expression increased in colonic mucosa 6 h after irradiation.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2020.110134