title: ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells.
abstract: The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.
authors: School of Life Sciences, Jilin University, Changchun, China.
authors: D
authors: D
authors: Wang
authors: School of Life Sciences, Jilin University, Changchun, China.
authors: T Q
authors: TQ
authors: Guo
authors: State Key Laboratory of Theoretical and Computational Chemistry, Jilin University, Changchun, China.
authors: Z Y
authors: ZY
authors: Wang
authors: School of Life Sciences, Jilin University, Changchun, China.
authors: J H
authors: JH
authors: Lu
authors: School of Life Sciences, Jilin University, Changchun, China.
authors: D P
authors: DP
authors: Liu
authors: School of Life Sciences, Jilin University, Changchun, China.
authors: Q F
authors: QF
authors: Meng
authors: School of Life Sciences, Jilin University, Changchun, China.
authors: J
authors: J
authors: Xie
authors: Faculty of Science, National University of Singapore, Singapore.
authors: X L
authors: XL
authors: Zhang
authors: School of Life Sciences, Jilin University, Changchun, China.
authors: Y
authors: Y
authors: Liu
authors: School of Life Sciences, Jilin University, Changchun, China.
authors: L S
authors: LS
authors: Teng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000302:isolation & purification; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D045304:Cytochromes c / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D019695:Glycyrrhizic Acid / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016716:PC12 Cells / Q000145:classification / Q000166:cytology / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000302:isolation & purification; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000302:isolation & purification
chemical_list: D000893:Anti-Inflammatory Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009025:Morpholines; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D018698:Glutamic Acid; D019695:Glycyrrhizic Acid; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one