Ghrelin Antagonized 1-Methyl-4-Phenylpyridinium (MPP+)-Induced Apoptosis in MES23.5 Cells

Abstract

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) acting to stimulate growth hormone release. In the previous study, we have observed the neuroprotective effects of ghrelin on dopaminergic neurons in vivo in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -treated Parkinson's disease mice. In order to illustrate the underlying mechanisms, in the present study, we conducted our experiment in vitro in 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells that could express GHS-R1a. Ten- to 1,000-micromol/L MPP(+) treatment caused decreased cell viability, with increased lactate dehydrogenase leakage. A 200-micromol/L MPP(+) treatment was chosen to do the further experiments. MES23.5 cells treated with 200 micromol/L MPP(+) showed decreased mitochondrial transmembrane potential, an elevated level of reactive oxidative species production and activation of caspase-3. Additionally, these cells also showed apoptotic morphological changes. Pretreatment with different doses of ghrelin (10(-12)-10(-7) mol/L) could abolish the MPP(+)-induced apoptotic changes in a dose-dependent manner. These results suggested that ghrelin could antagonize MPP(+)-induced apoptosis in MES23.5 cells. The protective effects of ghrelin involved the restoration of mitochondria function.

Wnt3a protects SH-SY5Y cells against 6-hydroxydopamine toxicity by restoration of mitochondria function

“…Cell viability was expressed as a percentage of the absorbance from control cells. The toxic effects of 6-OHDA to SH-SY5Y cells were also detected by measuring the leakage of the cytosolic enzyme LDH to the culture medium using a colorimetric LDH assay kit (KeyGen, China) according to the manufacturer’s instructions [17]. Briefly, after 100 μM 6-OHDA added, 20 μl of cell medium were added into basic solution to measure extracellular LDH activity, which could catalyze the conversion of lactate to pyruvate, which then reacted with 2,4-dinitrophenylhydrazine to give the brownish red color.…”

Nesfatin-1 protects dopaminergic neurons against MPP+/MPTP-induced neurotoxicity through the C-Raf–ERK1/2-dependent anti-apoptotic pathway

“…Many studies have demonstrated that apoptosis induced by mitochondrial dysfunction plays important roles in the development of PD678, indicating that the prevention of apoptosis could be a therapeutic strategy for PD. In our previous studies, we reported that ghrelin, which is secreted by X/A-like cells in the gastric glands, showed neuroprotective effects on dopaminergic neurons exposed to the toxin 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) both in vivo and in vitro via an anti-apoptotic effect mediated by the ghrelin-protein kinase C (PKC) signaling pathway91011.…”

Recombinant adenovirus-mediated expression of GHS-R1a in HEK 293 cells

“…Recent studies have reported that ghrelin could inhibit apoptosis in several cell lines via GHS-R1a [16][17][18] . Our previous study has also revealed the neuroprotective effects of ghrelin on dopaminergic neurons [7,8] . Zeenat Atcha et al have reported that ghrelin receptor agonists can elicit pro-cognitive effects in recognition and spatial learning and memory tests [19] .…”

“…Therefore, in the present study, adenovirus vectors were employed to transfer the target gene. Previous studies have demonstrated that ghrelin, a newly identified 28-amino acid brain-gut peptide, can inhibit apoptosis in Parkinson's disease (PD) models both in vitro and in vivo, through its receptor: growth hormone secretagogue receptor type 1a (GHS-R1a) [7,8] . Besides, it has been reported that ghrelin receptor agonists elicit pro-cognitive effects and can enhance spatial learning and memory.…”