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.
Merritt, A.J.; Potten, C.S.; Watson, A.J.; Loh, D.Y.; Nakayama, K.; Nakayama, K.; Hickman, J.A. Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. J. Cell Sci 1995, 108, 2261–2271.
[3]
Maharwal, J.; Samarth, R.M.; Saini, R. Antioxidative effect of rajgira leaf extract in liver of swiss albino mice after exposure to different doses of gamma radiation. Phytother. Res 2005, 19, 717–720.
[4]
Mittal, A.; Pathania, V.; Agrawala, P.K.; Prasad, J.; Singh, S.; Goel, H.C. Influence of podophyllum hexandrum on endogenous antioxidant defense system in mice: Possible role in radioprotection. J. Ethnopharmacol 2001, 76, 253–262.
[5]
Kondo, Y.; Ishigami, A.; Kubo, S.; Handa, S.; Gomi, K.; Hirokawa, K.; Kajiyama, N.; Chiba, T.; Shimokado, K.; Maruyama, N. Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl phosphorofluoridate in the liver. FEBS Lett 2004, 570, 57–62.
[6]
Linster, C.L.; van Schaftingen, E. Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J 2007, 274, 1–22.
[7]
Fujita, T.; Uchida, K.; Maruyama, N. Purification of senescence marker protein-30 (SMP30) and its androgen independent decrease with age in the rat liver. Biochim. Biophys. Acta 1998, 1116, 122–128.
[8]
Ishigami, A.; Fujita, T.; Handa, S.; Shirasawa, T.; Koseki, H.; Kitamura, T.; Enomoto, N.; Sato, N.; Shimosawa, T.; Maruyama, N. Senescence marker protein-30 knockout mouse liver is highly susceptible to tumor necrosis factor-alpha- and Fas-mediated apoptosis. Am. J. Pathol 2002, 161, 1273–1281.
[9]
Matsuyama, S.; Kitamura, T.; Enomoto, N.; Fujita, T.; Ishigami, A.; Handa, S.; Maruyama, N.; Zheng, D.; Ikejima, K.; Takei, Y.; et al. Senescence marker protein-30 regulates Akt activity and contributes to cell survival in Hep G2 cells. Biochem. Biophys. Res. Commun 2004, 321, 386–390.
[10]
Koike, K.; Kondo, Y.; Sekiya, M.; Sato, Y.; Tobino, K.; Iwakami, S.I.; Goto, S.; Takahashi, K.; Maruyama, N.; Seyama, K.; et al. Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice. Am. J. Physiol. Lung. Cell. Mol. Physiol 2010, 298, L784–L792.
[11]
Park, J.K.; Ki, M.R.; Lee, H.R.; Hong, I.H.; Ji, A.R.; Ishigami, A.; Park, S.I.; Kim, J.M.; Chung, H.Y.; Yoo, S.E.; et al. Vitamin C deficiency attenuates liver fibrosis by way of up-regulated peroxisome proliferator-activated receptor-gamma expression in senescence marker protein 30 knockout mice. Hepatology 2010, 51, 1766–1777.
[12]
Park, J.K.; Lee, E.M.; Kim, A.Y.; Lee, E.J.; Min, C.W.; Kang, K.K.; Lee, M.M.; Jeong, K.S. Vitamin C deficiency accelerates bone loss inducing an increase in PPAR-γ expression in SMP30 knockout mice. Int. J. Exp. Pathol 2012, 93, 332–340.
[13]
Kondo, Y.; Inai, Y.; Sato, Y.; Handa, S.; Kubo, S.; Shimokado, K.; Goto, S.; Nishikimi, M.; Maruyama, N.; Ishigami, A. Senescence marker protein 30 functions as gluconolactonase in l-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. Proc. Natl. Acad. Sci. USA 2006, 103, 5723–5728.
[14]
Son, T.G.; Zou, Y.; Jung, K.J.; Yu, B.P.; Ishigami, A.; Maruyama, N.; Lee, J. SMP30 deficiency causes increased oxidative stress in brain. Mech. Ageing. Dev 2006, 127, 451–457.
[15]
Arai, K.Y.; Sato, Y.; Kondo, Y.; Kudo, C.; Tsuchiya, H.; Nomura, Y.; Ishigami, A.; Nishiyama, T. Effects of vitamin C deficiency on the skin of the senescence marker protein-30 (SMP30) knockout mouse. Biochem. Biophys. Res. Commun 2009, 385, 478–483.
[16]
Matsuu-Matsuyama, M.; Shichijo, K.; Okaichi, K.; Ishii, K.; Wen, C.Y.; Fukuda, E.; Nakayama, T.; Nakashima, M.; Okumura, Y.; Sekine, I. Sucralfate protects intestinal epithelial cells from radiation-induced apoptosis in rats. J. Radiat. Res. (Tokyo) 2006, 47, 1–8.
[17]
Bowen, J.M.; Gibson, R.J.; Cummins, A.G.; Keefe, D.M. Intestinal mucositis: The role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage. Support. Care. Cancer 2006, 14, 713–731.
[18]
Potten, C.S. Radiation and Gut; Potten, C.S., Hendry, J.H., Eds.; Elsevier Science: Amsterdam, The Netherlands, 1995; pp. 1–31.
[19]
Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R. Crypt base columnar stem cells in small intestines of mice are radioresistant. Gastroenterology 2012, 143, 1266–1276.
[20]
Potten, C.S. The significance of spontaneous and induced apoptosis in the gastrointestinal tract of mice. Cancer. Metastasis. Rev 1992, 11, 179–195.
[21]
Eble, M.J.; Lehnert, T.; Treiber, M.; Latz, D.; Herfarth, C.; Wannenmacher, M. Moderate dose intraoperative and external beam radiotherapy for locally recurrent rectal carcinoma. Radiother. Oncol 1998, 49, 169–174.
[22]
Coopersmith, C.M.; Gordon, J.I. Gamma-Ray-induced apoptosis in transgenic mice with proliferative abnormalities in their intestinal epithelium: Re-entry of villus enterocytes into the cell cycle does not affect their radioresistance but enhances the radiosensitivity of the crypt by inducing p53. Oncogene 1997, 15, 131–141.
[23]
Reed, J.C. Apoptosis and Cancer Chemotherapy; Hickman, J.A., Dive, C., Eds.; Humana Press: Totowa, MJ, USA, 1999; pp. 99–116.
[24]
Oltvai, Z.N.; Milliman, C.L.; Korsmeyer, S.J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993, 74, 609–619.
[25]
Brown, M. What causes the radiation gastrointestinal syndrome? Overview. Int. J. Radiat. Oncol. Biol. Phys 2008, 70, 799–800.
[26]
Jee, Y.H.; Jeong, W.I.; Kim, T.H.; Hwang, I.S.; Ahn, M.J.; Joo, H.G.; Hong, S.H.; Jeong, K.S. p53 and cell-cycle-regulated protein expression in small intestinal cells after fast-neutron irradiation in mice. Mol. Cell. Biochem 2005, 270, 21–28.
[27]
Wijsman, J.H.; Jonker, R.R.; Keijzer, R.; van de Velde, C.J.; Cornelisse, C.J.; van Dierendonck, J.H. A new method to detect apoptosis in paraffin sections: In situ end-labeling of fragmented DNA. J. Histochem. Cytochem 1993, 41, 7–12.
[28]
Kerr, J.F.; Winterford, C.M.; Harmon, B.V. Apoptosis. Its significance in cancer and cancer therapy. Cancer 1994, 73, 2013–2026.
Ijiri, K.; Potten, C.S. Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation. Br. J. Cancer 1983, 47, 175–185.
[31]
Hall, P.A.; Coates, P.J.; Ansari, B.; Hopwood, D. Regulation of cell number in the mammalian gastrointestinal tract: The importance of apoptosis. J. Cell Sci 1994, 107, 3569–3577.
