The Succinate Receptor as a Novel Therapeutic Target for Oxidative and Metabolic Stress-Related Conditions

We demonstrated that succinate receptor 1 is subject to complex N-glycosylation, the precise role of this posttranslational modification remains to be determined

Ana Carolina Ariza; Peter Meinardus T. Deen; Joris Hubertus Robben

2012

Scholarcy highlights

  • The sequencing of the human genome lead to the cloning, deorphanization, and characterization of many novel G proteincoupled receptors
  • We demonstrated that succinate receptor 1 is subject to complex N-glycosylation, the precise role of this posttranslational modification remains to be determined
  • In polarized renal Madin–Darby Canine Kidney cells, we found that succinate-induced temporal desensitization of the receptor, but that this did not involve significant internalization of the receptor from the plasma membrane
  • Using SUCNR1-specific shRNA, the succinate-induced expression of VEGF could be could be reduced in retinal pigment epithelium cells, confirming a role of SUCNR1 in the regulation of vascular adaptations in the retina
  • It was shown that SUCNR1 activation in the luminal membrane of the macula densa cells triggers renin release from the JGA via a similar mechanism, in this case SUCNR1 serves as a sensor for succinate in the pro-urine rather than in the blood
  • Similar downstream signaling pathways were identified in other tissues or cell types: in SUCNR1-positive adipocytes, succinate inhibits lipolysis in a pertussis toxin-dependent manner, demonstrating that SUCNR1 signaling inhibits cAMP formation that is induced by lipolytic hormones
  • The synergistic effect of succinate receptor 1 and toll-like receptors may contribute significantly to the release of high levels of tumor necrosis factor α, increasing inflammation, renal epithelial apoptosis, and recruitment, binding, and migration of leukocytes

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