Inhibition of radiation-induced apoptosis via overexpression of SMP30 in Smad3-knockout mice liver.
Apoptosis occurs early after irradiation and may be a good indicator of radiation damages. Since elevated levels of TGF-beta are associated with radiation-induced inflammation, the null mice of Smad3, a key downstream mediator of TGF-beta, show accelerated healing of irradiated injury. In order to evaluate resistance to radiation-induced liver injuries in Smad3-null mice, we determined the occurrence of apoptosis and the expression of senescence marker protein-30 (SMP30), as an anti-apoptotic marker, after irradiation to the liver. The livers of Smad3-mutant mice were exposed to local irradiation of 15 gray, from a (60)Co-gamma radiation. One week after irradiation, in Smad3-KO mice, radiation-induced apoptosis was at lower levels compared to those of irradiated WT mice. These findings were well matched with the expression of CYP2E1, which plays a role in hepatic injuries produced by oxidative stress. In addition, antioxidant related protein, the SMP30 levels were reduced by gamma irradiation in both groups. Interestingly, the increased expression of SMP30 expression in Smad3-KO mice liver was preserved at a higher level than that of the WT mice after irradiation. Therefore, these results suggest that the interruption of TGF-beta signaling by deletion of Smad3 brings about inhibition of hepatic apoptosis after ionizing irradiation. Moreover, the protective effect to ionizing radiation might be in correlation with the overexpression of SMP30 in the Smad3-null mice, which may act as an anti-apoptotic signaling molecule. The alteration of SMP30 by interruption of Smad3 might be a useful therapeutic target and diagnostic marker for radiation-induced liver damages.
Jeong
Da-Hee
DH
Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea.
Goo
Moon-Jung
MJ
Hong
Il-Hwa
IH
Yang
Hai-Jie
HJ
Ki
Mi-Ran
MR
DO
Sun-Hee
SH
Ha
Jeoung-Hee
JH
Lee
Seung-Sook
SS
Park
Jin-Kyu
JK
Jeong
Kyu-Shik
KS
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000528:radiation effects
D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513324:Rgn protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse