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Selenoprotein M was differentially interacted the apoptosis-related
proteins in vitro and in vivo
Chang Joon Bae, Ji Soon Sin, Yong Kyu Kim, Chul Kyu Kim, Byung Guk Kim, Sun Bo
Shim, Seung Wan Jee, Su Hae Lee, Byoung Chun Lee, Mi Kyong Jang, Min Sun Kim, Su
Youn Yim, In Surk Jang*, Jung Sik Cho, Kab Ryong Chae and Dae Youn Hwang
Laboratory Animal Resources Team, National Institute of Toxicological Research,
Korea FDA, 5, Nokbun-dong, Eunpyng-gu, Seoul, 122-702, Korea, *Department of
Animal Science & Biotchnology, Jinju National University, Jinju 660-758, Korea
Selenoproteins are enzymes that contain selenium in the form of selenocystein in
their catalytic center. Until now, there were 25 known genes encoding selenoproteins in
the sequenced human genome. To exam whether Selenoprotein M (SelM) expression
and selenium treatment were effected on the expression level of the apoptosis proteins,
pCMV/hIDE fusion genes were overexpressed in the HEK 293 cell line and hSel-Tg rat.
Two transgenic mice were identified by PCR analysis using specific primers by
screening 28 newborn founder mice, and the GFP-hSelM fusion protein were
successfully detected on the protein level in the HEK 293 cell line and hSelM-Tg rat.
Also, it was also observed that p53 proteins were significantly changed in the HEK 293
cell under the condition of hSelM overexpression and selenuim treatment, while not
changed in the kidney tissue of SelM-Tg rat. Furthermore, one of the apoptosis-related
protein, Bax proteins, were significantly changed in the kidney of SelM-Tg rat under the
condition of hSelM overexpression and sel treatment, while not changed in the HEK
293 cell line. Finally, Bcl2 proteins in the HEK 293 cell were significantly decreased in
the hSelM transfectants, but hSelM-Tg rat were shown the different expression patterns
in the sel treated condition. These results suggest that SelM can differentially interacted
the was apoptosis-related proteins in vitro (tumor cell line) and in vivo (transgenic
tissue expressing SelM protein)
Key words: selenoprotein M, selenium, transgenic rat, antioxidant enzyme
Transgenic rat overexpressing human selenoprotein M was
significantly changed the concentration of antioxidant and H2O2, the
activity of antioxidant enzyme, and the composition of white blood cell
Daeyoun Hwang, Jisoon Sin, Minsun Kim, Suyoun Yim, Yongkyu Kim, Cheulkyu Kim,
Byoungguk Kim, Sunbo Shim, Seungwan Jee, Suhae Lee, Changjoon Bae, Byoungchun
Lee, Meekyung Jang, Jungsik Cho and Kabryong Chae
Laboratory Animal Resources Team, National Institute of Toxicological Research,
Korea FDA, Seoul 122-704, Korea
Selenoprotein M (SelM) was first reported as a 0.7-kb cDNA gene that encoded a
new selenoprotein identified from mammalian EST database, and might play a
suppressive or protective role in the pathology of patients with Alzheimer’s disease. In
order to examine the function of antioxidant protective in vivo, the new transgenic mice
was produced by the microinjection of human selenoprotein M cDNA into rat fertilized
egg and characterized the physiological features. Human SelM gene was successfully
expressed to transcript and protein in the CMV/GFP-hSelM Tg. This Tg rat showed the
different enzyme activity for antioxidant protein in the various tissues. In the response
of AAPH injection, Tg rats showed the lower level of antioxidant and H2O2 because the
activity of antioxidant enzyme was maintained higher level compare to non-Tg rat.
Furthermore, neutrophil-to-lyphocyte ratio was significantly increased in this Tg rat,
although corticosteron level was not changed in the both genotypes, respectively.
Finally, ERK signaling pathway was significantly induced in the brain of Tg rat under
the condition of selenium treatment. Therefore, these results suggested that the hSelM
transgenic rat might be useful for studying the relationship between the antioxidant
condition and disease, which shows a higher level of antioxidant condition in specific
tissues.
Key words : selenoprotein M, selenium, transgenic rat, antioxidant enzyme