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Title 

Translocation and oligomerization of Bax is regulated independently by activation of p38 MAPK and caspase-2 during MN9D dopaminergic neurodegeneration

 

MN9D 도파민성 신경세포의 사멸시 p38 MAPK와 Casapse-2에 의해 조절받는 Bax 단백질의 이동과 결합

Authors 

C K OhBaek Soo HanW S ChoiM B H YoudimY J Oh

Publisher 

Springer Verlag (Germany)

Issue Date 

2011

Citation 

Apoptosis, vol. 16, no. 11, pp. 1087-1100

Keywords 

6-HydroxydopamineBax oligomerizationCaspase-2P38 MAPK

Abstract 

Bax is translocated into the mitochondrial membrane and oligomerized therein to initiate mitochon-drial apoptotic signaling. Our previous study indicated that reactive oxygen species (ROS)-mediated activation of mitogen-activated protein kinase (MAPK) and caspase is critically involved in 6-hydroxydopamine (6-OHDA)-mediated neurodegeneration. Here, we specifically attempted to examine whether and how these death signaling pathways may be linked to Bax translocation and oligomerization. We found that 6-OHDA treatment triggered translocation and oligomerization of Bax onto the mitochondria in MN9D dopaminergic neuronal cells. These events preceded cyto-chrome c release into the cytosol. Cross-linking assay revealed that co-treatment with a ROS scavenger or a pan-caspase inhibitor inhibited 6-OHDA-induced Bax oligo-merization. Among several candidates of ROS-activated MAPKs and caspases, we found that co-treatment with PD169316 or VDVAD specifically inhibited 6-OHDA-induced Bax oligomerization, suggesting critical involvement of p38 MAPK and caspase-2. Consequently, overexpression of a dominant negative form of p38 MAPK or a shRNA-mediated knockdown of caspase-2 indeed inhibited 6-OHDA-induced Bax oligomerization. However, activation of p38 MAPK and caspase-2 was independently linked to oligomerization of Bax. This specificity was largely confirmed with a Bax 6A7 antibody known to detect activated forms of Bax on the mitochondria. Taken together, our data suggest that there is an independent amplification loop of Bax translocation and oligomerization via caspase-2 and p38 MAPK during ROS-mediated dopaminergic neurodegeneration.

ISSN 

1360-8185

Link 

http://dx.doi.org/10.1007/s10495-011-0627-8

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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