scholarly journals Metformin alleviates high glucose-mediated oxidative stress in rat glomerular mesangial cells by modulation of p38 mitogen-activated protein kinase expression in vitro

2012 ◽  
Vol 12 (1) ◽  
pp. 520-526 ◽  
Author(s):  
XIN-MING YAO ◽  
SHAN-DONG YE ◽  
CHUN-CHUN XIAO ◽  
JUN-FEI GU ◽  
DI YANG ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
High Glucose ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Glomerular Mesangial Cells ◽  
Mitogen Activated Protein ◽  
Kinase Expression

scholarly journals Oxidative stress inhibits MEKK1 by site-specific glutathionylation in the ATP-binding domain

2004 ◽  
Vol 381 (3) ◽  
pp. 675-683 ◽  
Author(s):  
Janet V. CROSS ◽  
Dennis J. TEMPLETON
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Cysteine Residue ◽  
Binding Domain ◽  
Mitogen Activated Protein Kinase ◽  
Atp Binding ◽  
Cysteine Oxidation ◽  
Mitogen Activated Protein ◽  
In Cells

Many intracellular signalling events are accompanied by generation of reactive oxygen species in cells. Oxidation of protein thiol groups is an emerging theme in signal-transduction research. We have found that MEKK1 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase kinase 1], an upstream activator of the SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, is directly inhibited by cysteine alkylation using NEM (N-ethylmaleimide). The related kinase, ASK1 (apoptosis signal-regulating kinase 1), was not inhibited, but was instead activated by NEM. Inhibition of MEKK1 requires a single unique cysteine residue (Cys1238) in the ATP-binding domain of MEKK1. Oxidative stress induced by menadione (2-methyl-1,4-naphthoquinone) also inhibited MEKK1, but activated ASK1, in cells. MEKK1 inhibition by menadione also required Cys1238. Oxidant-inhibited MEKK1 was re-activated by dithiothreitol and glutathione, supporting reversible cysteine oxidation as a mechanism. Using various chemical probes, we excluded modification by S-nitrosylation or oxidation of cysteine to sulphenic acid. Oxidant-inhibited MEKK1 migrated normally on non-reducing gels, excluding the possibility of intra- or inter-molecular disulphide bond formation. MEKK1 was inhibited by glutathionylation in vitro, and MEKK1 isolated from menadione-treated cells was shown by MS to be modified by glutathione on Cys1238. Our results support a model whereby the redox environment within the cell selectively regulates stress signalling through MEKK1 versus ASK1, and may thereby participate in the induction of apoptosis by oxidative stress.

scholarly journals Cellular signaling by endothelin peptides: pathways to the nucleus.

1992 ◽  
Vol 2 (10) ◽  
pp. S116
Author(s):  
M S Simonson ◽  
Y Wang ◽  
M J Dunn
Keyword(s):  
Protein Kinase ◽  
Mesangial Cells ◽  
Regulatory Peptides ◽  
Mitogen Activated Protein Kinase ◽  
Activator Protein 1 ◽  
Glomerular Mesangial Cells ◽  
Short Term ◽  
Activator Protein ◽  
Mitogen Activated Protein

Endothelins (ET) are potent regulatory peptides that evoke diverse responses in glomerular mesangial cells. These include short-term actions, such as contraction and secretion, and long-term, adaptive responses, such as cell growth. Although much attention has been focused on the second messenger cascades, which govern short-term effects, the pathways of cytosolic and nuclear signaling, which effect long-term changes, remain unclear. Several distal signaling events by ET receptors have been characterized in rat mesangial cells. These include activation of a cytosolic protein kinase, mitogen-activated protein kinase and an inducible transcription factor, activator protein-1 (AP-1). This review focuses on the activation of mitogen-activated protein kinase and activator protein-1 by ET and discusses the potential role of these third and fourth messengers in controlling long-term cellular adaptations. Characterization of these and other cytosolic and nuclear signals should provide important insights into the pleiotropic actions of ET peptides.

scholarly journals Norcantharidin Enhances High Concentrations of Fetal Bovine Serum-Induced Apoptosis in Human Mesangial Cells by Regulating the Mitogen-Activated Protein Kinase Signaling Pathway

2019 ◽  
Vol 44 (6) ◽  
pp. 1339-1351
Author(s):  
Kun Ye ◽  
Qiao-Yu Wei ◽  
Teng-Xiang Long ◽  
Hong-Guang He ◽  
Yun-Feng Huang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Bovine Serum ◽  
Mesangial Cells ◽  
Fetal Bovine Serum ◽  
Mitogen Activated Protein Kinase ◽  
Human Mesangial Cells ◽  
Mitogen Activated Protein ◽  
Fetal Bovine ◽  
Protein Kinase Signaling

Aim: This study aimed to investigate the effect of norcantharidin (NCTD) on human mesangial cells (HMCs) apoptosis in vitro and further examine its molecular mechanism. Methods: HMCs were divided into 5 groups: control group, 25% fetal bovine serum (FBS)-treated group, and NCTD groups (NCTD [2.5, 5 and 10 µg/mL] + 25% FBS, respectively). Cell proliferation was determined by MTT assay, while apoptosis was evaluated by Hoechest 33258 staining, the level of cytochrome c, immunohistochemistry, and apoptotic-related proteins/gene expression. Results: Cell viability was inhibited in NCTD-treated HMCs in a dose-dependent manner. The number of apoptotic cells and the content of cytochrome c were significantly increased by NCTD treatment but that of mitochondrial membrane was decreased. Moreover, the expression of bcl-2 and caspase-3 was prompted by NCTD, but the expression of bax, MMP-2, and MMP-9 in 25% FBS-treated HMCs was inhibited. In addition, NCTD markedly unregulated the expression of apoptosis-related gene/protein, including p-Erk1/2, phosphorylated-Jun N-terminal kinase (JNK), p-p38, and p53. Conclusion: NCTD enhances 25% FBS-treated HMC apoptosis in vitro, and this effect may be attributed to the modulation of the ERK, JNK, and p38 mitogen-activated protein kinase signaling pathways.

Sign in / Sign up

Export Citation Format

Share Document