A novel role for the calcium sensing receptor in rat diabetic encephalopathy.
Cell Physiol Biochem
; 35(1): 38-50, 2015.
Article
em En
| MEDLINE
| ID: mdl-25547907
ABSTRACT
BACKGROUND:
Diabetic encephalopathy is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations ([Ca(2+)]i) at its onset. The calcium sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic encephalopathy remains unclear.METHODS:
In this study, diabetic rats were modeled by STZ (50 mg/kg). At the end of 4, 8 and 12 weeks, the CaSR expression in hippocampus was analyzed by Western blot. In neonatal rat hippocampal neurons, the [Ca(2+)]i was detected by laser scanning confocal microscopy, the production of reactive oxygen species (ROS) in mitochondria, the level of NO and the mitochondrial transmembrane potential were measured by MitoSOX, DAF-FM and JC-1, respectively.RESULTS:
Our results showed in hippocampal neurons treated with high glucose, CaSR regulated [Ca(2+)]i through the PLC-IP3 pathway. CaSR expression was decreased and was involved in the changes in [Ca(2+)]i. Mitochondrial membrane potential, NO release and expression of p-eNOS decreased, while the production of ROS in mitochondria increased.CONCLUSION:
Down-regulation of CaSR expression was accompanied by neuronal injury, calcium disturbance, increased ROS production and decreased release of NO. Up-regulation of CaSR expression attenuated these changes through a positive compensatory protective mechanism to inhibit and delay diabetic encephalopathy in rats.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Detecção de Cálcio
/
Diabetes Mellitus Experimental
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article