Further Evidence of the Melatonin Calmodulin Interaction: Effect on CaMKII Activity

International Journal of Molecular Sciences

卷:23

Javier Velázquez-Moctezuma¹  Rosa Estrada-Reyes²  Gloria Benítez-King³  Julián Oikawa-Sala³  Jesús Argueta³  Héctor Solís-Chagoyán³  Luis A. Constantino-Jonapa³ 

[1] Clínica de Trastornos del Sueño, Universidad Autónoma Metropolitana, Iztapalapa, Mexico City 09340, Mexico;

[2] Laboratorio de Fitofarmacología, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Mexico City 14370, Mexico;

[3] Laboratorio de Neurofarmacología, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Mexico City 14370, Mexico;

关键词: calmodulin;    melatonin;    calmodulin kinase II;    colocalization;    hippocampus;   

DOI  :  10.3390/ijms23052479

来源: DOAJ

【 摘 要 】

Melatonin (MEL) is a pleiotropic indolamine that reaches multiple intracellular targets. Among these, MEL binds to calmodulin (CaM) with high affinity. In presence of Ca²⁺, CaM binds to CaM-dependent kinase II (CaMKII). The Ca²⁺-CaM/CaMKII pathway regulates a myriad of brain functions in different cellular compartments. Evidence showing the regulation of this cellular pathway by MEL is scarce. Thus, our main objective was to study the interaction of MEL with CaM and its effects on CaMKII activity in two microenvironments (aqueous and lipidic) naturally occurring within the cell. In addition, colocalization of MEL with CaM in vivo was explored in mice brain hippocampus. In vitro CaM-MEL interaction and the structural conformations of CaM in the presence of this indoleamine were assessed through electrophoretic mobility and isoelectric point. The functional consequence of this interaction was evaluated by measuring CaMKII activity. Ca²⁺-CaM-MEL increased the activity of CaMKII in aqueous buffer but reduced the kinase activity in lipid buffer. Importantly, MEL colocalizes in vivo with Ca²⁺-CaM in the hippocampus. Our evidence suggests that MEL regulates the key cellular Ca²⁺-CaM/CaMKII pathway and might explain why physiological MEL concentrations reduce CaMKII activity in some experimental conditions, while in others it drives biological processes through activation of this kinase.

【 授权许可】

Unknown