Apelin‑13 attenuates ER stress‑associated apoptosis induced by MPP+ in SH‑SY5Y cells

Apelin‑13, a neuropeptide that acts as a ligand for a putative receptor related to the angiotensin II type receptor, elicits neuroprotective effects in numerous neurological conditions, such as Huntington's disease and cerebral ischemia. Parkinson's disease (PD), one of the most prevalent neurodegenerative diseases, is caused by damage to neurons in the brain; however, the underlying mechanism remains unclear. The present study explored the effects of apelin‑13 on SH‑SY5Y human neuroblastoma cells treated with 1‑methyl‑4‑phenylpyridine (MPP+). Cell growth, cell viability, and apoptosis were measured by real‑time cell analysis, the Cell Counting Kit‑8 assay, and flow cytometry, respectively. In addition, the expression levels of extracellular signal‑regulated kinase (ERK) 1/2, p38 mitogen‑activated protein kinase (MAPK), glucose‑regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and cleaved caspase‑12 were assessed by western blotting. MPP+ treatment decreased the viability of SH‑SY5Y cells and increased their apoptosis; however, these changes were attenuated by pretreatment with apelin‑13. Treatment with MPP+ for 24 h significantly increased the expression levels of phospho‑ERK1/2, phospho‑p38, GRP78, CHOP, and cleaved caspase‑12 in SH‑SY5Y cells. Pretreatment with apelin‑13 significantly attenuated the upregulation of GRP78, CHOP and cleaved caspase‑12 in MPP+‑treated SH‑SY5Y cells, and significantly enhanced the expression levels of phospho‑ERK1/2. Taken together, the present results support a model in which apelin‑13 inhibits MPP+‑induced apoptosis of SH‑SY5Y cells by decreasing the expression of GRP78, CHOP, and cleaved caspase‑12, and by increasing the expression of phospho‑ERK1/2. The present findings suggest that apelin‑13 may be useful for the treatment of PD.