The Effect Of MAPK/JNK In Non-apoptotic Programmed Cell Death

Background and Purpose: Cell death is an important physiological and pathological phenomenon of Ihe vital process of organisma multicelluaris. The developing and survival of organisma multicelluaris depend on the balance between cell proliferation and cell death.As the balance is interrupted, embryonic dysplasia.degenerative desease and cancer will become reality.Cell death include positive Programmed Cell Death and passive non-Programmed Cell Death,the latter to be necrosis. Several new dead phaenotypes of PCD discovered recently called generally Non-apoptotic Programmed Cell Death,except classical apoptosis.Up to now, both physiological and biochemical mechanism is not clear yet,although many studies on Non-apoptotic Programmed Cell Death is carried out. Mitogen activated protein kinases (MAPKs) are the important signal transduction systym in vivo. MAPK signaling pathway is the crosstalk or the final common pathway, and many cellular processes are mediated, for example, growth, development, division,diffrenttiation, apoptosis and other cellular interactions,etc.This study on the basis of construction of Non-apoptotic Programmed Cell Death model was designed to reveal cell morphological features espasially through scanning electron microscope and stressed to approach the relations between MAPK and Non-apoptotic Programmed Cell Death.Material and Methods:1. Samples were obtained from neurons of rats cortical cultured in vitro and interfered by KA through KA/AMPA receptor, as KA is designed 5 groups for dose(5,10,50,100,500μmol/l).Corpusclular morphology will be observed through light microscope and scanning electron microscope when the non-apoptotic programmed death cell is deteced by tunnel and DNA ladder; 2.①The expressions of MAPK family members JNK and p38 phosphory-lated protein in cells dealed with KA is detected by immu nohistochemistry and western blotting,②To detect surviaval rate with MTT and to observe morphology through micoroscope so to know the changes of dealed cells with SP600125 and SB203580 in advance of KA;3.Data were analysised with ANOVA and t-test All experimental dat were processed by SPSS 10.0 software in computer. There was a statistica significance when P＜0.05 occurred.Results:Cytoplasmic vacuolation was observered and Cellular memebrane is intact as KA induced neuron.At the same time, tunel are negative and typical apoptotic DNA ladder was not seen.The expression of phoshorylated JNK is increasing obviously and the increation is accompanied by the dose of KA,which could be inhibited by SP600125.The expression of phoshorylated P38 protein is not increasing obviously with KA, and P38 could be inhibited by SB203580. Cell survival rate is lower with KA than the control.and vacuolated cells are higher.P-JNK and p-P38 express most in nuclear withKA.Conclusion:Non-apoptotic Programmed Cell Death of neuron induced by KA is mediated by MAPK/JNK, which can be inhibited by SP600125 that is a protector from Non-apoptotic Programmed Cell Death, and there is no relations of expressions between the increation of p-JNK and the dose of KA; MAPK/P38 was not found to link directly with Non-apoptotic Programmed Cell Death of neuron induced by KA.