Increased Susceptibility of Radiation-Induced Intestinal Apoptosis in SMP30 KO Mice

Moon-Jung Goo,Eun-Mi Lee,Jin-Kyu Park,Ah-Young Kim,Meeyul Hwang,Il-Hwa Hong,Kyu-Shik Jeong,Eun-Joo Lee

doi:10.3390/ijms140611084

Abstract

Recently, senescence marker protein-30 (SMP30) knockout (KO) mice have been reported to be susceptible to apoptosis, however, the role of SMP30 has not been characterized in the small intestine. The aim of the present study is to investigate the role of SMP30 in the process of spontaneous and γ-radiation-induced apoptosis in mouse small intestine. Eight-week-old male wild-type (WT) mice and SMP30 KO mice were examined after exposure to 0, 1, 3, 5, and 9 Gy of γ-radiation. Apoptosis in the crypts of the small intestine increased in the 0 to 5 Gy radiated SMP30 KO and WT mice. Radiation-induced apoptosis and the BAX/Bcl-2 ratio in the SMP30 KO mice were significantly increased in comparison to each identically treated group of WT mice (p < 0.05). The levels of spontaneous apoptosis in both WT and KO mice were similar (p > 0.05), indicating that increased apoptosis of crypt cells of SMP30 KO by irradiation can be associated with SMP30 depletion. These results suggested that SMP30 might be involved in overriding the apoptotic homeostatic mechanism in response to DNA damage.

Highlights

Apoptosis is programmed cell death induced by a cellular “decision” to commit to a particular cell fate after cellular damage [1]
Typical morphological appearance of apoptosis in the crypts of the mouse small intestines was observed in both irradiated Senescence marker protein-30 (SMP30) WT and KO mice with hematoxylin and eosin (H&E) staining (Figure 1)
Radiation-induced crypt apoptosis was more significantly increased in the SMP30 KO mice compared with the WT mice at each dose of irradiation

Summary

Introduction

Apoptosis is programmed cell death induced by a cellular “decision” to commit to a particular cell fate after cellular damage [1]. Radiation injuries result from the increased production of reaction oxygen species (ROS) such as superoxide anions, hydroxyl radicals, hydrogen peroxide, peroxyls, and alkoxy radicals. These reactive molecules may play an important role in the initiation and propagation of free radical chain reactions, inducing potentially severe damages to cells [3]. Ishigami et al reported that SMP30 has anti-apoptotic characteristics by demonstrating that hepatocytes of SMP30 KO mice showed an increased susceptibility to tumor necrosis factor-a (TNF-a) and Fas induced apoptosis in both in vitro and in vivo studies [8]

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