Neurochemical Research

, Volume 32, Issue 1, pp 115–124

Cis-Parinaric Acid Effects, Cytotoxicity, c-Jun N-terminal Protein Kinase, Forkhead Transcription Factor and Mn-SOD Differentially in Malignant and Normal Astrocytes

Authors

  • Ayesha Zaheer
    • Department of NeurosurgeryUniversity of Iowa Hospital and Clinics
    • Department of NeurosurgeryUniversity of Iowa Hospital and Clinics
  • Timothy C. Ryken
    • Department of NeurosurgeryUniversity of Iowa Hospital and Clinics
  • Vincent C. Traynelis
    • Department of NeurosurgeryUniversity of Iowa Hospital and Clinics
Original Paper

DOI: 10.1007/s11064-006-9236-2

Cite this article as:
Zaheer, A., Sahu, S.K., Ryken, T.C. et al. Neurochem Res (2007) 32: 115. doi:10.1007/s11064-006-9236-2

Abstract

cis-Parinaric acid (c-PNA), a natural four conjugated polyunsaturated fatty acid, increases free radical production and it is preferentially cytotoxic to malignant glial cells compared to normal astrocytes in-vitro. In order to explain the increased cytotoxicity of c-PNA in malignant glial cells, we compared the effects of c-PNA on the oxidative stress-dependent signal transducing events in 36B10 cells, a malignant rat astrocytoma cell line, and in fetal rat astrocytes. Our results show that c-PNA treatment in 36B10 cells caused a persistent activation of c-Jun N-terminal protein kinase (JNK) at RNA and protein levels. Specific inhibitors of the kinase significantly reversed the cytotoxicity of c-PNA. Additionally, c-PNA caused the phosphorylated inactivation of forkhead transcription factor-3a (FKHR-L1, FOXO3a) and drastically decreased the activity of mitochondrial superoxide dismutase (Mn-SOD) that protects cells from oxidative stress. On the other hand, identical c-PNA treatments in normal astrocytes increased the dephosphorylated activation of FKHR-L1, maintained activity of Mn-SOD and failed to phosphorylate JNK. Taken together, the results imply that a selective activation of JNK and the opposite regulation of FKHR-L1 and Mn-SOD contribute to the differential cytotoxicity of c-PNA in malignant and normal glial cells.

Keywords

cis-Parinaric acidAstrocytesMalignant astrocytesGliomaForehead transcription factor-3a (FKHR-L1FOXO3a)Mitogen-activated protein kinases

Abbreviations

c-PNA

cis-Parinaric acid

SOD

Superoxide dismutase

JNK

c-Jun N-terminal protein kinase

FKHR

Forkhead transcription factor

RT-PCR

Reverse transcription-polymerase chain reaction

ELISA

Enzyme-linked immunosorbent assay

MTT

3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

MAPK

Mitogen-activated protein kinase

Copyright information

© Springer Science+Business Media, LLC 2006