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.

Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells

Life Sciences ◽  
2000 ◽  
Vol 68 (6) ◽  
pp. 635-645 ◽  
Author(s):  
Daisuke Inui ◽  
Masanori Yoshizumi ◽  
Yuki Suzaki ◽  
Kazuyoshi Kirima ◽  
Koichiro Tsuchiya ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Human Mesangial Cells ◽  
Endothelin 1 ◽  
Mitogen Activated Protein

scholarly journals Identification of RAS-Mitogen-Activated Protein Kinase Signaling Pathway Modulators in an ERF1 Redistribution® Screen

2006 ◽  
Vol 11 (4) ◽  
pp. 423-434 ◽  
Author(s):  
Charlotta Grånäs ◽  
Betina Kerstin Lundholt ◽  
Frosty Loechel ◽  
Hans-Christian Pedersen ◽  
Sara Petersen Bjørn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Kinase Inhibitors ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
A Cell ◽  
Protein Kinase Signaling

The RAS-mitogen-activated protein kinase (MAPK) signaling pathway has a central role in regulating the proliferation and survival of both normal and tumor cells. This pathway has been 1 focus area for the development of anticancer drugs, resulting in several compounds, primarily kinase inhibitors, in clinical testing. The authors have undertaken a cell-based, high-throughput screen using a novel ERF1 Redistribution® assay to identify compounds that modulate the signaling pathway. The hit compounds were subsequently tested for activity in a functional cell proliferation assay designed to selectively detect compounds inhibiting the proliferation of MAPK pathway-dependent cancer cells. The authors report the identification of 2 cell membrane-permeable compounds that exhibit activity in the ERF1 Redistribution® assay and selectively inhibit proliferation of MAPK pathway-dependent malignant melanoma cells at similar potencies (IC50 =< 5 μM). These compounds have drug-like structures and are negative in RAF, MEK, and ERK in vitro kinase assays. Drugs belonging to these compound classes may prove useful for treating cancers caused by excessive MAPK pathway signaling. The results also show that cell-based, high-content Redistribution® screens can detect compounds with different modes of action and reveal novel targets in a pathway known to be disease relevant.

scholarly journals Lipoprotein (a) stimulates mitogen activated protein kinase in human mesangial cells

FEBS Letters ◽  
1998 ◽  
Vol 441 (2) ◽  
pp. 205-208 ◽  
Author(s):  
Ulrich F. Mondorf ◽  
Albrecht Piiper ◽  
Martina Herrero ◽  
Michael Bender ◽  
Ernst H. Scheuermann ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Human Mesangial Cells ◽  
Lipoprotein A ◽  
Mitogen Activated Protein

scholarly journals Endothelin-1 (1-31) activates p38 Mitogen-Activated Protein Kinase in Human Mesangial Cells

2000 ◽  
Vol 82 ◽  
pp. 124
Author(s):  
Yuki Suzaki ◽  
Daisuke Inui ◽  
Kazuyoshi Kirima ◽  
Yuichi Ozawa ◽  
Koichiro Tsuchiya ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Human Mesangial Cells ◽  
Endothelin 1 ◽  
Mitogen Activated Protein

scholarly journals PreproEndothelin-1 Expression in Human Mesangial Cells: Evidence for a p38 Mitogen-Activated Protein Kinase/Protein Kinases-C—Dependent Mechanism

2001 ◽  
Vol 12 (6) ◽  
pp. 1137-1150
Author(s):  
MARCO FOSCHI ◽  
ANDREY SOROKIN ◽  
PHILLIP PRATT ◽  
ANN MCGINTY ◽  
GIORGIO LA VILLA ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Mesangial Cells ◽  
Regulatory Elements ◽  
Mitogen Activated Protein Kinase ◽  
Human Mesangial Cells ◽  
Proinflammatory Mediators ◽  
Mitogen Activated Protein ◽  
Intracellular Ca ◽  
Factor Α

Abstract. Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal inflammation. This study investigated the mechanisms underlying the synergistic upregulation of preproET-1 gene expression in human mesangial cells after co-stimulation with thrombin and tumor necrosis factor α (TNFα). Whereas thrombin induced a moderate upregulation of preproET-1 mRNA, co-stimulation with TNFα resulted in a strong and protracted upregulation of this mRNA species. Thrombin+TNFα-induced upregulation of preproET-1 expression was found to require p38 mitogen-activated protein kinase and protein kinases C, whereas activation of extracellular signal-regulated kinase, c-Jun-N-terminal kinase, or intracellular Ca2+ release were not required. Actinomycin D chase experiments suggested that enhanced stability of preproET-1 mRNA did not account for the increase in transcript levels. PreproET-1 promoter analysis demonstrated that the 5′-flanking region of preproET-1 encompassed positive regulatory elements engaged by thrombin. Negative modulation of thrombin-induced activation exerted by the distal 5′ portion of preproET-1 promoter (-4.4 kbp to 204 bp) was overcome by co-stimulation with TNFα, providing a possible mechanism underlying the synergistic upregulation of preproET-1 expression by these two agonists. In conclusion, human mesangial cell expression of preproET-1 may be increased potently in the presence of two common proinflammatory mediators, thereby providing a potential mechanism for ET-1 production in inflammatory renal disease.

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