Neurochemical Research

, Volume 32, Issue 1, pp 115–124 | Cite as

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

  • Ayesha Zaheer
  • Shailendra K. Sahu
  • Timothy C. Ryken
  • Vincent C. Traynelis
Original Paper


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.


cis-Parinaric acid Astrocytes Malignant astrocytes Glioma Forehead transcription factor-3a (FKHR-L1 FOXO3a) Mitogen-activated protein kinases 



cis-Parinaric acid


Superoxide dismutase


c-Jun N-terminal protein kinase


Forkhead transcription factor


Reverse transcription-polymerase chain reaction


Enzyme-linked immunosorbent assay


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


Mitogen-activated protein kinase


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Ayesha Zaheer
    • 1
  • Shailendra K. Sahu
    • 1
  • Timothy C. Ryken
    • 1
  • Vincent C. Traynelis
    • 1
  1. 1.Department of NeurosurgeryUniversity of Iowa Hospital and ClinicsIowaUSA

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