Effects of electroconvulsive shock on the phosphorylation of DARPP-32 in rat striatum.
Dopamine- and cAMP-regulated phosphoprotein with molecular weight 32 kDa (DARPP-32) is a key integrative molecule in the dopaminergic and glutamatergic signaling pathways in the striatum. Electroconvulsive shock (ECS), which induces massive neuronal depolarization, can activate various signaling pathways. In this study we investigated whether ECS could affect the phosphorylation status of DARPP-32. Male Sprague-Dawley rats underwent ECS and were sacrificed by decapitation at 0, 2, 10, 60, and 180 min after treatment. The phosphorylations of Thr34 and Thr75 residues of DARPP-32 and Ser159 residue of cyclin-dependent kinase 5 (CDK5) were investigated in the striatum. The activity of protein phosphatase 1 (PP1) and the binding between DARPP-32 and PP1 were also analyzed. Thr34 phosphorylation of DARPP-32 increased immediately after ECS and this state was maintained for more than 60 min. The activity of PP1 decreased and the binding between PP1 and DARPP-32 increased in accordance with this phosphorylation pattern. However, the phosphorylation at Thr75 showed no significant change except for an initial transient decrease. The phosphorylation of CDK5, which is responsible for Thr75 phosphorylation of DARPP-32, did not exhibit significant fluctuations. Our findings indicate that ECS increases Thr34 phosphorylation of DARPP-32, and thus inhibits the activity of PP1.
Park
Hye-Jean
HJ
Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea.
Cui
Feng Ji
FJ
Roh
Jae Woo
JW
Jung
Young Chul
YC
Kim
Se Hyun
SH
Kim
Yong Sik
YS
Kang
Ung Gu
UG
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D004597:Electroshock; D008297:Male; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D054645:Protein Phosphatase 1