Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling.
J Biol Chem
; 287(13): 9694-9707, 2012 Mar 23.
Article
em En
| MEDLINE
| ID: mdl-22308028
ABSTRACT
The increase of apo-/holo-retinol-binding protein 4 (RBP4) concentrations has been found in subjects with renal dysfunction and even in diabetic patients with microalbuminuria. Holo-RBP4 is recognized to possess cytoprotective function. Therefore, we supposed that the relative increase in apo-RBP4 might induce cell damage. In this study, we investigated the signal transduction that activated apoptosis in response to the increase of apo-/holo-RBP4 concentration. We found that increase of apo-/holo-RBP4 concentration ratio delayed the displacement of RBP4 with "stimulated by retinoic acid 6" (STRA6), enhanced Janus kinase 2 (JAK2)/STAT5 cascade, up-regulated adenylate cyclase 6 (AC6), increased cAMP, enhanced JNK1/p38 cascade, suppressed CRBP-I/RARα (cellular retinol-binding protein/retinoic acid receptor α) expression, and led to apoptosis in HK-2 and human umbilical vein endothelial cells. Furthermore, STRA6, JAK2, STAT5, JNK1, or p38 siRNA and cAMP-PKA inhibitor reversed the repression of CRBP-I/RARα and apoptosis in apo-RBP4 stimulation. In conclusion, this study indicates that the increase of apo-/holo-RBP4 concentration may influence STRA6 signaling, finally causing apoptosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Sistema de Sinalização das MAP Quinases
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Proteínas Plasmáticas de Ligação ao Retinol
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article