Involvement of the Mitogen-activated Protein Kinase Family in Tetracaine-induced PC12 Cell Death

2002 ◽  
Vol 96 (5) ◽  
pp. 1191-1201 ◽  
Author(s):  
Zhiming Tan ◽  
Shuji Dohi ◽  
Jinen Chen ◽  
Yosiko Banno ◽  
Yoshinori Nozawa
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Pc12 Cells ◽  
Dna Fragmentation ◽  
Local Anesthetics ◽  
Caspase 3 ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Erk Phosphorylation ◽  
Mitogen Activated Protein

Background To explore whether cytotoxicity of local anesthetics is related to apoptosis, the authors examined how local anesthetics affect mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs)-stress-activated protein kinases, and p38 kinase, which are known to play important roles in apoptosis. Methods Cell death was evaluated using PC12 cells. Morphologic changes of cells, cellular membrane, and nuclei were observed. DNA fragmentation was electrophoretically assayed. Western blot analysis was performed to analyze phosphorylation of the MAPK family, cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase. Intracellular Ca2+ concentration was measured using a calcium indicator dye. Results Tetracaine-induced cell death was shown in a time- and concentration-dependent manner and characterized by nuclear condensation or fragmentation, membrane blebbing, and internucleosomal DNA fragmentation. Caspase-3 activation and phosphorylation of ERK, JNK, and p38 occurred in the cell death. PD98059, an inhibitor of ERK, enhanced tetracaine-induced cell death and JNK phosphorylation, whereas ERK phosphorylation was inhibited. Curcumin, an inhibitor of JNK pathway, attenuated the cell death. Increase of intracellular Ca2+ concentration was detected. In addition to the increase of ERK phosphorylation and the decrease of JNK phosphorylation, two Ca2+ chelators protected cells from death. Neither cell death nor phosphorylation of the MAPK family was caused by tetrodotoxin. Nifedipine did not affect tetracaine-induced apoptosis. Conclusions Tetracaine induces apoptosis of PC12 cells via the MAPK family. ERK activation protects cells from death, but JNK plays the opposite role. Toxic Ca2+ influx caused by tetracaine seems to be responsible for the cell death, but blocking of Na+ channels or L-type Ca2+ channels is unlikely involved in the tetracaine's action for apoptosis.

scholarly journals Platyphyllenone Induces Autophagy and Apoptosis by Modulating the AKT and JNK Mitogen-Activated Protein Kinase Pathways in Oral Cancer Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4211
Author(s):  
Yen-Tze Liu ◽  
Hsin-Yu Ho ◽  
Chia-Chieh Lin ◽  
Yi-Ching Chuang ◽  
Yu-Sheng Lo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Oral Cancer ◽  
Protein Expression ◽  
Caspase 3 ◽  
Therapeutic Option ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Cancer Proliferation ◽  
Mitogen Activated Protein

Platyphyllenone is a type of diarylheptanoid that exhibits anti-inflammatory and chemoprotective effects. However, its effect on oral cancer remains unclear. In this study, we investigated whether platyphyllenone can promote apoptosis and autophagy in SCC-9 and SCC-47 cells. We found that it dose-dependently promoted the cleavage of PARP; caspase-3, -8, and -9 protein expression; and also led to cell cycle arrest at the G2/M phase. Platyphyllenone up-regulated LC3-II and p62 protein expression in both SCC-9 and SCC-47 cell lines, implying that it can induce autophagy. Furthermore, the results demonstrated that platyphyllenone significantly decreased p-AKT and increased p-JNK1/2 mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner. The specific inhibitors of p-JNK1/2 also reduced platyphyllenone-induced cleavage of PARP, caspase-3, and caspase -8, LC3-II and p62 protein expression. These findings are the first to demonstrate that platyphyllenone can induce both autophagy and apoptosis in oral cancers, and it is expected to provide a therapeutic option as a chemopreventive agent against oral cancer proliferation.

scholarly journals Biotransformed blueberry juice protects neurons from hydrogen peroxide-induced oxidative stress and mitogen-activated protein kinase pathway alterations

2010 ◽  
Vol 104 (5) ◽  
pp. 656-663 ◽  
Author(s):  
Tri Vuong ◽  
Chantal Matar ◽  
Charles Ramassamy ◽  
Pierre S. Haddad
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Protein Kinase ◽  
Neurodegenerative Disorders ◽  
Mitogen Activated Protein Kinase ◽  
Antioxidant Enzyme Activities ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Blueberry Juice ◽  
Mitogen Activated Protein

A growing body of evidence supports the therapeutic effects of blueberry in neurodegenerative disorders. Biotransformation of blueberry juice by Serratia vaccinii bacteria increases its phenolic content and antioxidant activity. In neuronal cell culture, biotransformed blueberry juice (BJ) significantly increased the activity of antioxidant enzymes, namely catalase and superoxide dismutase. Moreover, BJ protected neurons against H2O2-induced cell death in a dose-dependent manner. This associated with the upregulation of mitogen-activated protein kinase (MAPK) family enzymes p38 and c-Jun N-terminal kinase (JNK) activation, as well as with the protection of extracellular signal-regulated kinase (ERK1/2) and MAPK/ERK kinase (MEK1/2) activity loss induced by H2O2. The present studies demonstrate that BJ can protect neurons against oxidative stress possibly by increasing antioxidant enzyme activities and activating p38- and JNK-dependent survival pathways while blocking MEK1/2- and ERK1/2-mediated cell death. Thus, BJ may represent a novel approach to prevent and to treat neurodegenerative disorders, and it may represent a source of novel therapeutic agents against these diseases.

scholarly journals Activation of TRAP/Mediator Subunit TRAP220/Med1 Is Regulated by Mitogen-Activated Protein Kinase-Dependent Phosphorylation

2005 ◽  
Vol 25 (24) ◽  
pp. 10695-10710 ◽  
Author(s):  
Pradeep K. Pandey ◽  
T. S. Udayakumar ◽  
Xinjie Lin ◽  
Dipali Sharma ◽  
Paul S. Shapiro ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Specific Substrate ◽  
Dependent Manner ◽  
Erk Phosphorylation ◽  
Mitogen Activated Protein

ABSTRACT The TRAP/Mediator coactivator complex serves as a molecular bridge between gene-specific activators and RNA polymerase II. TRAP220/Med1 is a key component of TRAP/Mediator that targets the complex to nuclear hormone receptors and other types of activators. We show here that human TRAP220/Med1 is a specific substrate for extracellular signal-regulated kinase (ERK) of the mitogen-activated protein kinase (MAPK) family. We demonstrate that ERK phosphorylates TRAP220/Med1 in vivo at two specific sites: threonine 1032 and threonine 1457. Importantly, we found that ERK phosphorylation significantly increases the stability and half-life of TRAP220/Med1 in vivo and correlates with increased thyroid hormone receptor-dependent transcription. Furthermore, ERK phosphorylates TRAP220/Med1 in a cell cycle-dependent manner, resulting in peak levels of expression during the G2/M phase of the cell cycle. ERK phosphorylation of ectopic TRAP220/Med1 also triggered shuttling into the nucleolus, thus suggesting that ERK may regulate TRAP220/Med1 subnuclear localization. Finally, we observed that ERK phosphorylation of TRAP220/Med1 stimulates its intrinsic transcriptional coactivation activity. We propose that ERK-mediated phosphorylation is a regulatory mechanism that controls TRAP220/Med1 expression levels and modulates its functional activity.

scholarly journals Phosphorylation of p38 Mitogen-Activated Protein Kinase Downstream of Bax-Caspase-3 Pathway Leads to Cell Death Induced by High d-Glucose in Human Endothelial Cells

Diabetes ◽  
2001 ◽  
Vol 50 (6) ◽  
pp. 1472-1481 ◽  
Author(s):  
Hironori Nakagami ◽  
Ryuichi Morishita ◽  
Kei Yamamoto ◽  
Shin-ichi Yoshimura ◽  
Yoshiaki Taniyama ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Protein Kinase ◽  
Caspase 3 ◽  
Mitogen Activated Protein Kinase ◽  
Human Endothelial Cells ◽  
Mitogen Activated Protein
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