Calycopterin Promotes Survival and Outgrowth of Neuron-Like PC12 Cells by Attenuation of Oxidative- and ER-Stress-Induced Apoptosis along with Inflammatory Response
- 21 November 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in Chemical Research in Toxicology
- Vol. 24 (12), 2280-2292
- https://doi.org/10.1021/tx200420a
Abstract
There is mounting evidence implicating the role of oxidative stress induced by reactive oxygen species (ROS) in neurodegenerative disease, including Alzheimer’s disease. Herein we investigated the neuroprotective potential of a natural flavonoid, calycopterin, against H2O2-induced cell death in differentiated PC12 cells. We pretreated PC12 cells with 25, 50, and 100 μM calycopterin followed by the addition of H2O2 as an oxidative stress agent. We measured cell viability by the MTT test and found that 50 μM is the best protective concentration of calycopterin. Moreover, we measured six different parameters of neurite outgrowth. Interestingly, we found that calycopterin not only protects PC12 cells against H2O2-induced apoptosis but also defends against the destructive effect of oxidative stress on the criteria of neural differentiation. Calycopterin decreased ER stress-associated proteins including calpain and caspase-12, and suppressed ERK, JNK, and p38 MAPK phosphorylation. Moreover, calycopterin inhibited H2O2-induced nuclear translocation of nuclear factor-κB, a known regulator of a host of genes involved in specific stress and inflammatory responses. This observation was perfectly in agreement with the decrease of COX-2 and TNF-α levels. Calycopterin reduced intracellular ROS levels and increased catalase activity. The protective effect of this compound could represent a promising approach for the treatment of neurodegenerative diseases.Keywords
This publication has 47 references indexed in Scilit:
- Calycopterin, an immunoinhibitory compound from the extract of Dracocephalum kotschyiPhytotherapy Research, 2008
- Drug discovery from medicinal plantsLife Sciences, 2005
- Aspirin Prevents Apoptosis and NF-κB Activation Induced by H2O2in HeLa CellsFree Radical Research, 2003
- Mitochondrial reactive oxygen species in cell death signalingBiochimie, 2002
- Energy Metabolism, Oxidative Stress and Neuronal Degeneration in Alzheimer's DiseaseNeurodegeneration, 1996
- Reactive oxygen species in living systems: Source, biochemistry, and role in human diseaseAmerican Journal Of Medicine, 1991
- [43] Malondialdehyde determination as index of lipid PeroxidationMethods in enzymology, 1990
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- Identity of Calycopterin and ThapsinNature, 1935
- The anthelminthic constituent of the leaves of Calycopteris floribundaBiochemical Journal, 1934