The mechanism of oxygen free radical/JNK inducing nerve injury after different degrees of intermittent hypoxia in rats
WANG Gong-Yang, GUO Xia, DIAO Ya-Ning, LI Lin, HAN Xiao-Qiang, ZHANG Fen-Fen
Chinese Journal of Clinical Anatomy ›› 2013, Vol. 31 ›› Issue (1) : 75-80.
The mechanism of oxygen free radical/JNK inducing nerve injury after different degrees of intermittent hypoxia in rats
Objective To investigate the mechanisms of oxygen free radical/JNK signaling pathway on nerve injury after different degree of intermittent hypoxia (IH) in rats. Methods one hundred and sixty Male Sprague-Dawley rats were randomly divided into four groups: control group（n=40），mild intermittent hypoxia group（n=40）, moderate intermittent hypoxia group（n=40），severe intermittent hypoxia group（n=40）. Rats in the control group were exposed in the air，the three intermittent hypoxia groups were exposed respectively in different intermittent hypoxia conditions:100 ml/L，75 ml/L and 50 ml/L; 8-hour-intermittent hypoxia everyday; the duration of experiment 2, 4, 6 and 8 weeks, respectively. The morphological changes were observed by electron microscopy；the malondialdehyde (MDA) contents in cortex were measured with spectrophotometry；the expressions of phosphorylated JNK and c-fos proteins were detected with immunohistochemistry and Western-Blot. The quantity of apoptotic cells was measured by terminal deoxynucleotidyl transfernase medicated nick end labeling (TUNEL) method. Results Compared with the control group，the ultrastructure of nerve cell nucleus was injured more severely and the phosphorylated JNK and c-fos expressions and TUNEL-positive cells numbers increased obviously in a time-dependant manner. Moreover, the abovementioned changes were more significant in severe intermittent hypoxia group. The MDA level，phosphorylated JNK and c-fos expressions and TUNEL-positive cells numbers reached peak at 6 weeks in the mild and moderate intermittent hypoxia groups and there were no significant difference between the two group； The MDA level，phosphorylated JNK and c-fos expressions and TUNEL-positive cells numbers reached peak at 8 weeks in severe intermittent hypoxia group and there was significant difference when compared with the mild or moderate intermittent hypoxia groups. Conclusions After intermittent hypoxia，oxygen free radical activated ERK1/2 signaling pathway played an important role in the process of nerve cell apoptosis by regulating c-fos expression.
Intermittent hypoxia / MAP-activated protein kinases / Immunohistochemistry / Western blot / Rat
[1] Kim EK，Choi EJ． Pathological roles of MAPK signaling pathways in human diseases
[J]. Biochim Biophys Acta，2010，1802( 4) : 396-405.
[2] Smith WW, Gorospe M, Kusiak JW. Signaling mechanisms underlying a beta toxicity: potential therapeutic targets for Alzheimer’sdisease
[J]. CNS Neurol Disord Drug Targets, 2006, 5(3): 355-361.
[3] Takeyama K, Jung B, Shim JJ, et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke
[J]. Am Physiol Lung CellMol Physiol, 2001, 280(1):L165-L172.
[4] Yoshizum M, Abe JI, Haendeler J, et al. Src and Cas mediate JNK activation but not ERK1 /2 and p38 Kinases by reactive oxygen species
[J]. Biol Chem, 2000, 275(16): 11706-11712.
[5] Coughlin SR, Mawdsley L, Mugarza JA, et al. Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome
[J]. Eur Heart，2004, 25(9)：735-741.
[6] Jun J, Savransky V, Nanayakkara A, et al. Intermittent hypoxia has organ-specific effects on oxidative stress
[J]. Physiol Regul Integr Comp Physiol, 2008，295(4):R1274-1281.
[7] Guan QH, Pei DS, Liu XM，et al. Neuroprotection against ischemic brain injury by SP600125 via suppressing the extrinsic and intrinsic pathways of apoptosis
[J]. Brain research, 2006, 1092(1):36-46.
[8] Ferrandi C, Ballerio R, Gaillard P, et al. Inhibition of c-Jun N-terminal kinase decreases cardiomyocyte apoptosis and infarct size aftermyocardial ischemia and reperfusion in anaesthetized rats
[J]. Pharmaco, 2004, 142(6): 953-960.
[9] Svatikova A, Work R, Lerman Lo, et al. Oxidative stressing obstructive sleep aponea
[J]. Eur Heart, 2005, 26(22): 2435-2439.
[10] D'Autréaux B,Toledano MB. ROS as signalling molecules:mechanisms that generate specificity in ROS homeostasis
[J].Nat Rev Mol Cell Biol, 2007, 8(10):813-824.
[11] Hong HY, Kim BC. Mixed lineage kinase 3 connects reactive oxygen species to c-Jun NH2-terminal kinase-induced mitochondrial apoptosis in genipin-treated PC3 human prostate cancer cells
[J].Biochem Biophys Res Commun, 2007, 62(2):307-312.
[12]Kim EM, Yang HS, Kang SW, et al. Amplification of the gamma- rra-diation-induced cell death pathway by reactive oxygen species in human U937 cells
[J].Cell Signal, 2008, 20(5):916-924.
[13] 孙琳, 刘爱芬, 李义召, 等.银杏叶制剂对脑缺血再灌注后热休克蛋白、c-fos表达的影响
[J].中国病理生理杂志，2005，21(12)：2427-2430.
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