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- Expression of Inducible Nitric Oxide Synthase and Nitric Oxide Mediated Apoptosis in Neuronal PC12 Cells after Lipopolysaccharide/Tumor Necrosis Factor-/Interferon- Treatment.
- Jiyeon Kim, Jiyoung Kim, Kuseong Kang, Eunkyoung Kwak, Jiyoung Park, Taein Park, Yoonkyung Sohn
- Korean J Pathol. 2002;36(4):249-256.
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Abstract
PDF - BACKGROUND
Inducible nitric oxide synthase (iNOS) has been detected in a number of pathologic conditions in the central nervous system. This study was investigated the patterns of iNOS expression in the neuronal PC12 cell and the effects of nitric oxide on the apoptosis of PC12 cells.
METHODS
The stimulating agents for induction of iNOS expression in PC12 cells were bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-), and interferon-gamma (IFN-).
RESULTS
The expression iNOS mRNA and protein in PC12 cells stimulated with LPS/TNF-/IFN- were profoundly increased. The expression of iNOS mRNA arose at 6 hours, peaked at 12 hours, and declined to 48 hours after LPS/TNF-/ IFN- treatment. iNOS protein was increased up to 24 hours in LPS/TNF-/IFN- treated PC12 cells while the expression of nNOS was unaffected. Accumulation of NO derivatives in the culture media was markedly increased at least at up to 48 hours after LPS/TNF-/IFN- treatment. The induction of iNOS expression and NO production in differentiated PC12 cells was correlated with apoptotic cell death judged by transmission electron microscopy and DNA fragmentation from the results of the Terminal deoxynucleotidyl-transferase-mediated dUDP biotin nick end-labeling (TUNEL) method. After treatment with NOS inhibitor, N-monomethylarginine (NMMA), a profound decrease in NO production by LPS/TNF-/IFN- treated PC12 cells was noted. And the LPS/TNF-/IFN- induced apoptosis was prevented by the NMMA treatment.
CONCLUSIONS
From the above results it is concluded that the expression of iNOS in differentiated PC12 cells is induced by the combined application of LPS, TNF-, and IFN-. And the apoptosis of cultured PC12 cells is mediated by iNOS-derived NO.
- Lipopolysaccharide/Interferon-gamma Induced Nitric Oxide Production in C6 Glioma Cells: Modulation by Dexamethasone.
- Jong Heun Shin, Ku Seong Kang, Ji Yeoun Kim, Sun Zoo Kim, Ji Young Park, Eun Kyoung Kwak, Yoon Kyung Sohn
- Korean J Pathol. 2002;36(6):406-411.
- 1,942 View
- 42 Download
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Abstract
PDF
- BACKGROUND
Glial cell-derived nitric oxide (NO), and its regulation has significant implications for central nervous system pathophysiology. The aim of the present study was to see the production of NO in lipopolysaccharide (LPS)/interferon-gamma (IFN-)-treated C6 glioma cells and the effect of dexamethasone on NO production and apoptosis of LPS/IFN--treated C6 glioma cells.
METHODS
The apoptosis of LPS/IFN- treated C6 glioma cell was examined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method and the production of NO in culture medium was measured. The expression of iNOS mRNA was examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The effect of the N-monomethyl L-arginine (NMMA) and dexamethasone on the apoptosis and NO production was also examined.
RESULTS
Inducible nitric oxide synthase (iNOS) mRNA and NO production were markedly increased in LPS/IFN--treated C6 glioma cells. The expression of iNOS mRNA arose at 3 hours, peaked at 12 hours, and declined 24 hours after LPS/IFN--treatment. Accumulation of NO derivatives in the culture media was increased at least upto 48 hours after LPS/IFN-. The induction of iNOS expression and NO production in LPS/IFN--treated C6 cells was correlated with apoptotic cell death judged by TUNEL staining. After treatment of NMMA, one of the NOS inhibitors, NO production and apoptosis were markedly decreased. Dexamehasone treatment suppressed the NO production by concentration depenedent manner.
CONCLUSIONS
From the above results it is concluded that the LPS/IFN- induced apoptosis of C6 cells is mediated by iNOS-derived NO and NO production and apoptosis was suppressed by dexamethasone.
- Expression of Tumor Necrosis Factor-alpha, Interleukin-1beta and Inducible Nitric Oxide Synthase after Stereotaxic Injection of Lipopolysaccharide in Rat Hippocampus.
- Hoon Kyu Oh, Ku Seong Kang, Ji Yeon Kim, Eun Kyoung Kwak, Jung Wan Kim, Ji Young Park, Yoon Kyung Sohn
- Korean J Pathol. 2004;38(3):157-164.
- 1,879 View
- 24 Download
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Abstract
PDF
- BACKGROUND
Brain inducible nitric oxide synthase (iNOS) might be detectable in several pathologic conditions, and it is thought to play an important role in their pathophysiology. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are believed to be essential factors of iNOS induction of the brain.
METHODS
After intrahippocampal stereotaxic injection of lipopoly-saccharide (LPS), the rat brains were removed at 6, 12 and 24 h. The rat brain tissues were examined to clarify the expression patterns of TNF-alpha, IL-1beta and iNOS.
RESULTS
The inflammatory cells which were stained with anti-TNF-alpha antibody, appeared in 6 h and increased for 24 h after LPS injection. The iNOS positive cells appeared after 12 h of LPS injection. A semiquantitative analysis of reverse transcription-polymerase chain reaction (RT-PCR) revealed that the TNF-alpha and IL-1beta mRNA arose at 1 h, peaked at 6 h and then declined until 48 h after LPS injection. The iNOS mRNA arose after 6 h, peaked at 12 h, and declined until 48 h after LPS injection.
CONCLUSIONS
We conclude that the induction of inflammatory events by intrahippocampal injection of LPS activates TNF-alpha and IL-1beta secretion, and this is followed by an induction of iNOS expression. TNF-alpha and IL-1beta seem to be related with iNOS expression in brain inflammation.
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