p38 MAPK is involved in CB2 receptor-induced apoptosis of human leukaemia cells

AbstractCannabinoids have been shown to inhibit the growth of a broad spectrum of tumour cells. However, the molecular mechanisms involved in that effect have not been completely elucidated. Here, we investigated the possible involvement of mitogen-activated protein kinases (MAPKs) in CB2 receptor-induced apoptosis of human leukaemia cells. Results show that stimulation of the CB2 receptor leads to p38 MAPK activation and that inhibition of this kinase attenuates CB2 receptor-induced caspase activation and apoptosis. These findings support a role for p38 MAPK in CB2 receptor-induced apoptosis of human leukaemia cells

Papel fisiológico de los nucleótidos extracelulares en el sistema nervioso central: señalización vía receptores P2X y P2Y

In the last few years nucleotide receptors, the ionotropic P2X1-7 subunits and the metabotropic P2Y1, 2, 4, 6, 11, 12, 13, 14, have acquired an excepcional importance due to their strategic location in organs and tissues, their great variety along with the complexity of the associated signalling pathways and the first evidence of the serious alterations entailed in their dysfunctions. Our group has been pioneer in the characterization of these receptors in the nervous system, where we defined their location and functionality. The abundant presence, at a presynaptic level, of P2X3 and P2X7 should be emphasized, where by means of calcium intake they induce neurotransmitter exocytosis, such as glutamate, GABA, catecholamines and acetylcholine among others, as described in previous works by our group. In addition, they induce an extensive remodeling of the terminal’s cytoskeleton and exocytotic mechanisms through CaMKII and they can interact widely with other ionotropic and metabotropic receptors co-existing in nearby areas. Neural cells also exhibit the presence of most P2Y receptors signalling through a large variety of intracellular cascades. Recently we have demostrated that P2Y metabotropic receptors of the sub-family activated by ADP, especially P2Y13, are connected with the signalling towards GSK3 and â-catenin, opening new ways of understading the nucleotide function in survival and maintenance of neural cells. In addition both P2X and P2Y receptors play a role in early developmental stages and neural maturation where their function has to be fully understanded. Nucleotide receptors are also very abundant in glial cells, and our group has shown that most P2Y receptors are present and fully functional in cultured astrocytes, where, depending on the subtype receptor they activate a large variety of signalling cascades.En los ultimos anos los receptores de nucleotidos, receptores ionotropicos P2X1-7 y metabotropicos P2Y1, 2, 4, 6, 11, 12, 13, 14, han adquirido una importancia excepcional debido a su localizacion estrategica en organos y tejidos, a su gran variedad junto con la complejidad de vias de senalizacion a las que estan asociados y a las primeras evidencias de importantes alteraciones debidas a su mal funcionamiento. Nuestro grupo ha sido pionero en la caracterizacion estos receptores en el sistema nervioso, donde definimos su localizacion y su funcionalidad. La abundante presencia, a nivel presinaptico, de las subunidades P2X3 y P2X7 debe ser resaltada, donde gracias a la entrada de calcio inducen la exocitosis de varios neurotransmisores, como glutamato, GABA, catecolaminas y acetilcolina entre otros, como ha sido descrito por nuestro grupo en trabajos previos. Ademas, estos receptores inducen una profunda remodelacion del citoesqueleto de las terminales nerviosas y de los mecanismos exocitoticos a traves de la CaMKII y pueden interactuar con otros receptores ionotropicos y metabotropicos co-existentes en sus cercanias. La mayoria de los receptores P2Y tambien estan presentes en las celulas nerviosas, activando vias de senalizacion a traves de una gran variedad de cascadas intracelulares. Recientemente hemos demostrado que los receptores metabotropicos P2Y pertenecientes a la sub-familia de receptores activados por ADP, especialmente el P2Y13, estan conectados con la senalizacion hacia GSK3 y ƒÀ-catenina, lo que abre nuevas vias para la comprension de la funcion de los nucleotidos en la supervivencia y el mantenimiento de las celulas nerviosas. Ademas, tanto los receptores P2X como los P2Y juegan un papel en los estadios iniciales del desarrollo y en la maduracion neuronal donde su funcion aun ha de ser plenamente comprendida. Los receptores de nucleotidos son tambien muy abundantes en las celulas gliales, y nuestro grupo ha demostrado que la mayoría de los receptores P2Y están presentes y son plenamente funcionales en astrocitos en cultivo, donde, dependiendo del subtipo de receptor, activan una gran variedad de cascadas de señalización