Format

Send to

Choose Destination
J Neurochem. 2015 Nov;135(3):466-78. doi: 10.1111/jnc.13233. Epub 2015 Sep 2.

Resveratrol prevents cadmium activation of Erk1/2 and JNK pathways from neuronal cell death via protein phosphatases 2A and 5.

Author information

1
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing, China.
2
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
3
Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.

Abstract

Cadmium (Cd), a toxic environmental contaminant, induces neurodegenerative disorders. Resveratrol, a natural product, has been found to exert neuroprotective effects. However, little is known regarding the effect of resveratrol on Cd-evoked neurotoxicity. Here, we show that resveratrol effectively reversed Cd-elicited cell viability reduction, morphological change, nuclear fragmentation and condensation, as well as activation of caspase-3 in neuronal cells, implying neuroprotection against Cd-poisoning by resveratrol. Further research revealed that both c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases 1/2 (Erk1/2) were involved in the inhibitory effect of resveratrol on Cd-induced cell death, as selective inhibitors of Erk1/2 (U0126) and JNK (SP600125), or over-expression of dominant negative mitogen-activated protein kinase kinase 1 (MKK1) or dominant negative c-Jun potentiated resveratrol's prevention of Cd-induced phosphorylation of JNK and Erk1/2, as well as cell death in neuronal cells. Interestingly, resveratrol potently rescued the cells from Cd-induced suppression of protein phosphatases 2A (PP2A) and 5 (PP5) activity. Over-expression of PP2A or PP5 strengthened the inhibitory effects of resveratrol on Cd-induced activation of Erk1/2 and/or JNK, as well as cell death. The results indicate that resveratrol prevents Cd-induced activation of Erk1/2 and JNK pathways and neuronal cell death in part via activating PP2A and PP5. Our findings strongly support the notion that resveratrol may serve as a potential therapeutic agent in the prevention of Cd-induced neurodegenerative diseases.

KEYWORDS:

cadmium; mitogen-activated protein kinase; neuronal cells; protein phosphatase 2A; protein phosphatase 5; resveratrol

PMID:
26146868
DOI:
10.1111/jnc.13233
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center