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Study On The Role Of MAPK/ERK Signal Pathway In Non-apoptotic PCD

Posted on:2008-06-10Degree:MasterType:Thesis
Country:ChinaCandidate:Z W TanFull Text:PDF
GTID:2144360218460067Subject:Forensic medicine
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Backgrounds and purpose: Recently growing evidence suggests that the classic categorization pattern, apoptosis-necrosis, may not sort all the cell death form. Generally, a fatal impulse may promote the activations of more than one death pathway corresponding to cell death form. The form of cell death mainly depends on the speed activated of intracellular death pathway. In many cases, Caspase pathway runs faster than others, so apoptosis often occurs instead of the other programmed cell death. Upon caspase inhibition, the alternative death pathways, non-apoptotic programmed cell death ( non-apoptotic PCD ), such as, apoptosis-like cell death or necrosis-like cell death, also surface in vivo. They are involved in processes of non-apoptotic PCD, such as, autophagic cell death , cytoplasmic cell death, cell death of tumour necrosis factor (TNF) -mediated liver injury, Huntington's disease and amyotrophic lateral sclerosis etc.There is seldom report concerning non-apoptotic PCD, most of which refer to appearence form and morphological description of non-apoptotic PCD. Nevertheless, the intracellular signaling mechanism of non-apoptotic PCD remains largely unknow. Here we explore the expression of phosphorylation of ERK1/2 and P38 mitogen-activated protein kinase in the non-apoptotic PCD induced by KA, to identify which pathway is involved in this process. And the specific inhibitor, U0126,SB203580, block respectively two pathway to further identify signal pathway involved in it. Further study concerning the non-apoptotic PCD can be developed based on the study.Methods: The Embryonic cortical neurons of 15-17 day pregnant embyo SD rat were cultured till 7d. Non-apoptotic PCD-induced by KA were explored using TUNEL, DNA separated on agarose gels and scanning electron microscope to identify the non-apoptotic PCD. Non-apoptotic PCD neurons were harvested for determination of phosphorylation of ERK1/2 and P38 mitogen-activated protein kinase by Western Blotting analysis, respectively. Further the specific inhibitor, U0126,SB203580, block respectively two pathway to identify which pathway involved in non-apoptotic PCD .Results: Non-apoptotic PCD induced by KA was characteristic of small cytoplasmic vacuoles with the intact cellular membrane, and negtive results on TUNEL and DNA ladder detection methods. SEM images show that the neurons have a rough surface, on which the particles and frills exist. An activation of ERKl/2 is involved in KA-induced non-apoptotic PCD. U0126 inhibition group was able to blunt the expression of ERKl/2 in KA-induced non-apoptotic PCD, and has less particles than KA group, and cell survival rate has an increase trend. while SB203580 was not able to blunt non-apoptotic PCD.Conclusion: In our study, SEM images of non-apoptotic PCD induced by KA provide the morphological materials for non-apoptotic PCD in the first time. The novel finding of present study is that an activation of ERK2 is involved in KA-induced non-apoptotic PCD. And U0126, ERK1/2 specific inhibition, may play a role of protection from the non-apoptotic PCD .These data provide the first direct evidence for a role of ERK2 in mediating KA-induced non-apoptotic PCD. Further study concerning the mechanism of non-apoptotic PCD can be developed based on the study.
Keywords/Search Tags:Kainic acid, neuron, primary cell culture, non-apoptotic programmed cell death, MAPK/ERK
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