Activation of alpha 7 nicotinic acetylcholine receptor protects mice from radiation-induced intestinal injury and mortality.
Radiation-induced gastrointestinal syndrome occurs when the body is exposed to a high dose of radiation. Currently, safe and effective radioprotectants are not available. Apoptosis was reported to play a primary role in radiation-induced injury. Recent evidence suggests that stimulation of α7 nicotinic acetylcholine receptor (α7nAChR) prevents cell death by inhibition of apoptosis. In this study, we demonstrated that a single dose of PNU282987 (100 μg/kg, i.p.), a selective α7nAChR agonist, protected mice from intestinal injury and significantly improved survival when administered prior to lethal 8 Gy total body irradiation. In vitro, PNU282987 protected against 8 Gy radiation-induced cell death in human umbilical venous endothelial cells by inhibiting apoptosis. We conclude that activation of α7nAChR may provide a new therapeutic pathway for the treatment of radiation-induced damage and mortality.
a  Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;
Ji-Kuai
JK
Chen
Zhang-Peng
ZP
Li
Yun-Zi
YZ
Liu
Ting
T
Zhao
Xin-Bin
XB
Zhao
Min
M
Ni
Guo-Jun
GJ
Jiang
Fu-Ming
FM
Shen
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D051379:Mice; D011832:Radiation Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D014916:Whole-Body Irradiation; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000096:biosynthesis / Q000235:genetics*
D064569:alpha7 Nicotinic Acetylcholine Receptor