Title |
Cis-Parinaric Acid Effects, Cytotoxicity, c-Jun N-terminal Protein Kinase, Forkhead Transcription Factor and Mn-SOD Differentially in Malignant and Normal Astrocytes
|
---|---|
Published in |
Neurochemical Research, December 2006
|
DOI | 10.1007/s11064-006-9236-2 |
Pubmed ID | |
Authors |
Ayesha Zaheer, Shailendra K. Sahu, Timothy C. Ryken, Vincent C. Traynelis |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 10% |
Unknown | 9 | 90% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 3 | 30% |
Student > Doctoral Student | 2 | 20% |
Other | 1 | 10% |
Professor | 1 | 10% |
Lecturer | 1 | 10% |
Other | 2 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 4 | 40% |
Biochemistry, Genetics and Molecular Biology | 2 | 20% |
Medicine and Dentistry | 2 | 20% |
Chemistry | 1 | 10% |
Unknown | 1 | 10% |