Cannabinoid receptor 1 mediates high XXXX -induced apoptosis via endoplasmic reticulum stress in primary cultured @entity35 mesangial cells.

@entity1 @entity10027 @entity28 @entity1976 @entity2316 @entity2310 @entity21205 @entity12874 @entity4124 @entity14513 @entity25308 @entity35 @entity12353 @entity4026 @entity413 @entity454
The endocannabinoid system in animals and @entity1 is involved in the onset of diverse diseases, including @entity28 and @entity2316 , which is a major @entity454 characterized by high @entity413 (HG)-induced apoptosis of mesangial cells. @entity12353 induce physiological and behavioral effects by activating two specific receptors, cannabinoid receptor 1 (CB(1)R) and @entity10027 (CB(2)R). However, the pathophysiology of CB(1)R in @entity2316 has not been elucidated. We investigated the effects of HG on CB(1)R expression and its signaling pathways in primary cultured @entity35 mesangial cells. HG significantly increased CB(1)R mRNA and protein levels in a time-dependent manner and induced CB(1)R internalization. @entity4026 and @entity25308 ) were involved in the HG-induced increase in CB(1)R levels. Using a CB(1)R antagonist ( @entity14513 ) and CB(1) siRNA transfection, we showed that HG-induced CB(1)R is linked to apoptosis. Specifically, HG inhibited the expression of @entity21205 , but induced increases in endoplasmic reticulum (ER) stress proteins, including phosphorylated (p)-protein kinase-like ER-associated kinase, p-eukaryotic initiation factor 2a, p-activating transcription factor-4, and C/EBP homologous protein. In addition, HG increased the @entity2310 / @entity1976 ratio and increased the amounts of cleaved @entity12874 polymerase and @entity4124 . These apoptotic effects were prevented by @entity14513 and by the downregulation of CB(1)R expression by small interfering RNA. We propose a mechanism by which blockade of CB(1)R attenuates HG-induced apoptosis in @entity35 mesangial cells. Our findings suggest that blockade of CB(1)R may be a potential therapy in @entity2316 .
