title: Involvement of the ERK pathway in the protective effects of glycyrrhizic acid against the MPP+-induced apoptosis of dopaminergic neuronal cells.
abstract: Glycyrrhizic acid (GA), a major compound separated from Radix Glycyrrhizae, has been shwon to exert various biochemical effects, including neuroprotective effects. In the present study, we investigated the protective effects of GA against 1-methyl-4-phenylpyridinium (MPP+)‑induced damage to differentiated PC12 (DPC12) cells. Compared with the MPP+-treated cells, GA markedly improved cell viability, restored mitochondrial dysfunction, suppressed the overexpression of cleaved poly(ADP-ribose) polymerase (PARP), and suppressed the overproduction of lactate dehydrogenase (LDH) and intracellular Ca2+ overload. The protective effects of GA on cell survival were further confirmed in primary cortical neurons. GA markedly increased the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), as well as its migration from the cytoplasm to nucleus. PD98059, an inhibitor of ERK, blocked GA-enhanced ERK activation and reduced cell viability. However, pre-treatment with GA had no effects on the expression of phosphorylated AKT (p-AKT) and total AKT (t-AKT). These results indicate that the GA-mediated neuroprotective effects are associated with its modulation of multiple anti-apoptotic and pro-apoptotic factors, particularly the ERK signaling pathway. This study provides evidence supporting the use of GA as a potential therapeutic agent for the treatment of neurodegenerative diseases and neuronal injury.
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
authors.affiliation: College of Clinical Medicine, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Chunjia
authors.initials: C
authors.lastname: Kou
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Lu
authors.affiliation: College of Electronic Science and Engineering, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Lu
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Zhenzuo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D005260:Female; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D019695:Glycyrrhizic Acid; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D015655:1-Methyl-4-phenylpyridinium; D002118:Calcium