NITRIC OXIDE-INDUCED CELL DEATH OF PC12 CELLS

1999 ◽  
Vol 27 (5) ◽  
pp. A146-A146
Author(s):  
A. Price ◽  
G.C. Brown
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Pc12 Cells

scholarly journals Molecular mechanism of PC12 cell death evoked by sodium nitroprusside, a nitric oxide donor.

2008 ◽  
Vol 55 (2) ◽  
pp. 339-347 ◽  
Author(s):  
Magdalena Pytlowany ◽  
Joanna B Strosznajder ◽  
Henryk Jeśko ◽  
Magdalena Cakała ◽  
Robert P Strosznajder
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Sodium Nitroprusside ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Protein Level ◽  
Caspase 3 ◽  
Time Dependent ◽  
Dependent Manner ◽  
Parp 1

Nitric oxide (NO) is a potent extracellular and intracellular physiological messenger. However, NO liberated in excessive amounts can be involved in macromolecular and mitochondrial damage in brain aging and in neurodegenerative disorders. The molecular mechanism of its neurotoxic action is not fully understood. Our previous data indicated involvement of NO in the release of arachidonic acid (AA), a substrate for cyclo- and lipoxygenases (COX and LOX, respectively). In this study we investigated biochemical processes leading to cell death evoked by an NO donor, sodium nitroprusside (SNP). We found that SNP decreased viability of pheochromocytoma (PC12) cells in a concentration- and time-dependent manner. SNP at 0.1 mM caused a significant increase of apoptosis-inducing factor (AIF) protein level in mitochondria. Under these conditions 80% of PC12 cells survived. The enhancement of mitochondrial AIF level might protect most of PC12 cells against death. However, NO released from 0.5 mM SNP induced massive cell death but had no effect on protein level and localization of AIF and cytochrome c. Caspase-3 activity and poly(ADP-ribose) polymerase-1 (PARP-1) protein levels were not changed. However, PARP activity significantly decreased in a time-dependent manner. Inhibition of both COX isoforms and of 12/15-LOX significantly lowered the SNP-evoked cell death. We conclude that AIF, cytochrome c and caspase-3 are not responsible for the NO-mediated cell death evoked by SNP. The data demonstrate that NO liberated in excess decreases PARP-1 activity. Our results indicate that COX(s) and LOX(s) are involved in PC12 cell death evoked by NO released from its donor, SNP.

scholarly journals 15-Deoxy-Δ12,14-Prostaglandin J2Protects against Nitrosative PC12 Cell Death through Up-regulation of Intracellular Glutathione Synthesis

2004 ◽  
Vol 279 (44) ◽  
pp. 46263-46270 ◽  
Author(s):  
So-Young Lim ◽  
Jung-Hee Jang ◽  
Hye-Kyung Na ◽  
Shelly C. Lu ◽  
Irfan Rahman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Pc12 Cells ◽  
Nitrosative Stress ◽  
Apoptotic Cell ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Membrane Depolarization ◽  
Intracellular Glutathione ◽  
Induced Apoptosis

Nitrosative stress with subsequent inflammatory cell death has been associated with many neurodegenerative disorders. Expression of inducible nitric-oxide synthase and production of nitric oxide (NO) have been frequently elevated in many inflammatory disorders. NO can rapidly react with superoxide anion, producing more reactive peroxynitrite. In the present study, exposure of rat pheochromocytoma (PC12) cells to the peroxynitrite donor 3-morpholinosydnonimine hydrochloride (SIN-1) induced apoptosis, which accompanied depletion of intracellular glutathione (GSH), c-Jun N-terminal kinase activation, mitochondrial membrane depolarization, the cleavage of poly(ADP-ribose)polymerase, and DNA fragmentation. During SIN-1-induced apoptotic cell death, expression of inducible cyclooxygenase (COX-2), and peroxisome proliferator-activated receptor-γ (PPARγ) was elevated. SIN-1 treatment resulted in elevated production of 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2), an endogenous PPARγ activator. Preincubation with 15d-PGJ2rendered PC12 cells resistant to nitrosative stress induced by SIN-1. 15d-PGJ2fortified an intracellular GSH pool through up-regulation of glutamylcysteine ligase, thereby preventing cells from SIN-1-induced GSH depletion. The above findings suggest that 15d-PGJ2may act as a survival mediator capable of augmenting cellular thiol antioxidant capacity through up-regulation of the intracellular GSH synthesis in response to the nitrosative insult.

Apoptotic cell death triggered by nitric oxide in pancreatic beta-cells

Diabetes ◽  
1995 ◽  
Vol 44 (7) ◽  
pp. 733-738 ◽  
Author(s):  
H. Kaneto ◽  
J. Fujii ◽  
H. G. Seo ◽  
K. Suzuki ◽  
T. Matsuoka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death

Nitric Oxide Exposure of CC531 Rat Colon Carcinoma Cells Induces γ-glutamyltransferase which May Counteract Glutathione Depletion and Cell Death

2003 ◽  
Vol 37 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Nils-Erik Huseby ◽  
Nana Asare ◽  
Silje Wetting ◽  
Idun Merete Mikkelsen ◽  
Bente Mortensen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Colon Carcinoma ◽  
Carcinoma Cells ◽  
Glutathione Depletion ◽  
Rat Colon ◽  
Colon Carcinoma Cells

scholarly journals Cold Atmospheric Pressure Plasma-Activated Medium Induces Selective Cell Death in Human Hepatocellular Carcinoma Cells Independently of Singlet Oxygen, Hydrogen Peroxide, Nitric Oxide and Nitrite/Nitrate

2021 ◽  
Vol 22 (11) ◽  
pp. 5548
Author(s):  
Yan Li ◽  
Tianyu Tang ◽  
Haejune Lee ◽  
Kiwon Song
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Singlet Oxygen ◽  
Atmospheric Pressure ◽  
Atmospheric Pressure Plasma ◽  
Proliferative Effect ◽  
Huh7 Cells ◽  
Anti Cancer ◽  
Cold Atmospheric Pressure Plasma ◽  
Nitrite Nitrate

Cold atmospheric pressure plasma (CAP) and plasma-activated medium (PAM) induce cell death in diverse cancer cells and may function as powerful anti-cancer agents. The main components responsible for the selective anti-cancer effects of CAP and PAM remain elusive. CAP or PAM induces selective cell death in hepatocellular carcinoma cell lines Hep3B and Huh7 containing populations with cancer stem cell markers. Here, we investigated the major component(s) of CAP and PAM for mediating the selective anti-proliferative effect on Hep3B and Huh7 cells. The anti-proliferative effect of CAP was mediated through the medium; however, the reactive oxygen species scavenger N-acetyl cysteine did not suppress PAM-induced cell death. Neither high concentrations of nitrite or nitrite/nitrate nor a low concentration of H2O2 present in the PAM containing sodium pyruvate affected the viability of Hep3B and Huh7 cells. Inhibitors of singlet oxygen, superoxide anions, and nitric oxide retained the capacity of PAM to induce anti-cancer effects. The anti-cancer effect was largely blocked in the PAM prepared by placing an aluminum metal mesh, but not a dielectric PVC mesh, between the plasma source and the medium. Hence, singlet oxygen, hydrogen peroxide, nitric oxide, and nitrite/nitrate are not the main factors responsible for PAM-mediated selective death in Hep3B and Huh7 cells. Other factors, such as charged particles including various ions in CAP and PAM, may induce selective anti-cancer effects in certain cancer cells.

An Insight into the Role of Apoptosis and Autophagy in Nitric Oxide–Induced Articular Chondrocyte Cell Death

Cartilage ◽  
2020 ◽  
pp. 194760352097676
Author(s):  
Ekkapol Akaraphutiporn ◽  
Takafumi Sunaga ◽  
Eugene C. Bwalya ◽  
Wang Yanlin ◽  
Mwale Carol ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Western Blot ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Chondrocyte Apoptosis ◽  
Protective Mechanism ◽  
Autophagic Flux ◽  
Qpcr Analysis

Objective To investigate the role and characterize the molecular mechanisms regulating apoptosis and autophagy in nitric oxide (NO)–induced chondrocyte cell death. Design Cell apoptosis and autophagy were evaluated in chondrocytes treated with sodium nitroprusside (SNP) combined with the presence or absence of interleukin-1 beta (IL-1β) and nutrient-deprived conditions. The concentration of nitrite was determined by Griess reaction. Activation of apoptosis and autophagy were determined by immunocytochemistry, Western blot, and quantitative real-time polymerase chain reaction (qPCR) analysis. Flow cytometry and MTT assay were used to assess cell viability. Results Cotreatment of chondrocytes with SNP and IL-1β under nutrient-deprived condition potentially enhanced the effect of NO-induced cell death. Immunocytochemistry, Western blot, and qPCR analysis indicated that treatment of chondrocytes with SNP significantly reduced autophagic activity, autophagic flux, and multiple autophagy-related (Atg) genes expression. These findings were associated with an increase in ERK, Akt, and mTOR phosphorylation, whereas autophagy induction through mTOR/p70S6K inhibition by rapamycin significantly suppressed NO-induced cell apoptosis. Furthermore, the cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 activation in response to apoptosis was weakly detected. These results corresponded with a significant increase in apoptosis-inducing factor (AIF) expression, suggesting the involvement of the caspase-independent pathway. Conclusions These results demonstrate that in chondrocyte cultures with cells induced into an osteoarthritis state, NO inhibits autophagy and induces chondrocyte apoptosis mainly, but not completely through the caspase-independent pathway. Our data suggest that autophagy is a protective mechanism in the pathogenesis of osteoarthritis and could be proposed as a therapeutic target for degenerative joint diseases.

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