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Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling.

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/RAR? (cellular retinol-binding protein/retinoic acid receptor ?) 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/RAR? 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.

SUBMITTER: Chen CH

PROVIDER: S-EPMC3322976 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling.

Chen Chao-Hung CH Hsieh Tusty-Jiuan TJ Lin Kun-Der KD Lin Hsing-Yi HY Lee Mei-Yueh MY Hung Wei-Wen WW Hsiao Pi-Jung PJ Shin Shyi-Jang SJ

The Journal of biological chemistry 20120203 13

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-/hol ...[more]

PMID: 22308028

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Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling.

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Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling.

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