Apelin receptor homodimer inhibits apoptosis in vascular dementia

Exp Cell Res. 2021 Oct 1;407(1):112739. doi: 10.1016/j.yexcr.2021.112739. Epub 2021 Jul 31.

Abstract

Apelin receptor (APJ), a member of family A of the G protein-coupled receptors (GPCRs), is a potential pharmaceutical target for diseases of the nervous system. Our previous work revealed that human APJ can form a homodimer that has different functional characteristics than the monomer. To investigate the effects of APJ homodimers on neuroprotection in vascular dementia (VD), we established VD model in rats and treated the animals by injecting apelin-13 into the lateral ventricle. In addition, we established an oxygen-glucose deprivation/reoxygenation (OGD/R) model in SH-SY5Y cells treated with apelin-13. After apelin-13 stimulation in the VD rat, the level of APJ and APJ homodimer were elevated. Furthermore, APJ homodimer decreased the level of cleaved caspase-3 and cleaved caspase-9 via the Gαi3 and Gαq signaling pathway, thereby increasing the number of neurons and inhibiting apoptosis. Consequently, APJ homodimers may serve as a unique mechanism for neuroprotection against VD and provide new pharmaceutical targets for VD.

Keywords: Apelin receptor; Apelin-13; Apoptosis; Cerebral ischemia/reperfusion; Homodimer; Vascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apelin Receptors / metabolism*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Dementia, Vascular / drug therapy*
  • Dementia, Vascular / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology

Substances

  • Apelin Receptors
  • Intercellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled
  • apelin-13 peptide