scholarly journals Chronic Activation of Glomerular Mitogen-Activated Protein Kinases in Dahl Salt-Sensitive Rats

2000 ◽  
Vol 11 (1) ◽  
pp. 39-46
Author(s):  
AKINORI HAMAGUCHI ◽  
SHOKEI KIM ◽  
YASUKATSU IZUMI ◽  
HIROSHI IWAO
Keyword(s):  
Protein Kinases ◽  
Binding Activity ◽  
High Salt ◽  
Glomerular Injury ◽  
High Salt Diet ◽  
Mitogen Activated Protein Kinases ◽  
Salt Diet ◽  
Dna Binding Activity ◽  
Mitogen Activated Protein ◽  
Chronic Activation

Abstract. The in vivo role of mitogen-activated protein kinases (MAPK) in the development of glomerular injury is poorly understood. In the present study, glomerular MAPK activities, including extracellular signal-regulated kinases (ERK), c-Jun NH2-terminal kinases (JNK), and transcriptional factor, activator protein-1 (AP-1) were examined in glomerular injury of salt-induced hypertensive rats. Six-week-old Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were maintained on a high-salt (8.0% NaCl) diet for 1, 5, and 10 wk. In Dahl-S rats, as shown by in-gel kinase assay, an increase in BP by a high-salt diet was followed by chronic activation of glomerular ERK and JNK, which continued until 10 wk after a high-salt diet. Western blot analysis demonstrated a significant increase in the protein expression of glomerular ERK and JNK in Dahl-S rats fed a high-salt diet. As determined by gel-mobility shift assay, ERK and JNK activations were associated with an increase in glomerular AP-1 DNA binding activity. On the other hand, in Dahl-R rats fed a high-salt diet, BP remained normal throughout the experiments. However, glomerular ERK and JNK activities and AP-1 DNA binding activity in Dahl-R rats were not affected by 1 or 5 wk of a high-salt diet, but significantly increased by 10 wk of treatment with a high-salt diet, indicating that chronic sodium overload itself stimulated glomerular ERK and JNK and AP-1 activities. These kinase activations in both Dahl-S and Dahl-R rats were accompanied by an increase in urinary protein excretion and renal growth. These observations provide the first evidence that salt-sensitive hypertension causes chronic activation of glomerular ERK and JNK, probably leading to the activation of AP-1. Thus, glomerular MAPK may be responsible for the development of salt-induced glomerular injury.

scholarly journals Activation of glomerular mitogen-activated protein kinases in angiotensin II-mediated hypertension.

1998 ◽  
Vol 9 (3) ◽  
pp. 372-380 ◽  
Author(s):  
A Hamaguchi ◽  
S Kim ◽  
M Yano ◽  
S Yamanaka ◽  
H Iwao
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinases ◽  
Binding Activity ◽  
Ang Ii ◽  
Glomerular Injury ◽  
Mitogen Activated Protein Kinases ◽  
Dna Binding Activity ◽  
Induced Hypertension ◽  
Mitogen Activated Protein

The in vivo signal transduction pathway, responsible for hypertension-induced glomerular injury, remains to be clarified. In this study, the effect of angiotensin II (Ang II)-induced hypertension was examined on glomerular mitogen activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), and on glomerular transcription factors activator protein-1 (AP-1) and Sp 1. MAPK activities were determined by in-gel kinase assay. DNA binding activity of AP-1 and Sp 1 was determined by gel mobility shift assay. Continuous infusion of Ang II (1000 ng/kg per min, intravenously) to conscious rats rapidly increased BP, followed by the rapid and transient activation of glomerular p42 and p44 ERK and p46 and p55 JNK with the peak at 15 to 180 min. Glomerular AP-1 binding activity was increased 2.6-fold (P < 0.01) at 24 h after the start of Ang II infusion. Supershift analysis showed that the activated AP-1 complexes contained c-Fos and c-Jun proteins. On the other hand, glomerular Sp 1 DNA binding activity was not changed throughout 7 d of Ang II infusion. These results provided the first in vivo evidence that Ang II-induced hypertension causes the activation of glomerular ERK and JNK, leading to the activation of AP-1. Thus, ERK and JNK signaling cascades, via the activation of AP-1, may be implicated in the development of hypertension-induced glomerular injury.

scholarly journals Effects of high salt diet on NF‐KB and CREB DNA binding activity in heart, kidney and hypothalamus of SHR

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Qianhui Shang ◽  
HongWei Wang ◽  
Alexandre FR Stewart ◽  
Frans H. H. Leenen
Keyword(s):  
Dna Binding ◽  
Binding Activity ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dna Binding Activity

scholarly journals Bacteroides fragilis Enterotoxin Induces Sulfiredoxin-1 Expression in Intestinal Epithelial Cell Lines Through a Mitogen-Activated Protein Kinases- and Nrf2-Dependent Pathway, Leading to the Suppression of Apoptosis

2020 ◽  
Vol 21 (15) ◽  
pp. 5383
Author(s):  
Jong Ik Jeon ◽  
Jun Ho Choi ◽  
Keun Hwa Lee ◽  
Jung Mogg Kim
Keyword(s):  
Protein Kinases ◽  
Bacteroides Fragilis ◽  
Binding Activity ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Mitogen Activated Protein Kinases ◽  
Dna Binding Activity ◽  
Oxidative Damages ◽  
Epithelial Cell Lines ◽  
Mitogen Activated Protein

Enterotoxigenic Bacteroides fragilis is a causative agent of colitis and secrets enterotoxin (BFT), leading to the disease. Sulfiredoxin (Srx)-1 serves to protect from oxidative damages. Although BFT can generate reactive oxygen species in intestinal epithelial cells (IECs), no Srx-1 expression has been reported in ETBF infection. In this study, we explored the effects of ETBF-produced BFT on Srx-1 induction in IECs. Treatment of IECs with BFT resulted in increased expression of Srx-1 in a time-dependent manner. BFT treatment also activated transcriptional signals including Nrf2, AP-1 and NF-κB, and the Srx-1 induction was dependent on the activation of Nrf2 signals. Nrf2 activation was assessed using immunoblot and Nrf2-DNA binding activity and the specificity was confirmed by supershift and competition assays. Suppression of NF-κB or AP-1 signals did not affect the upregulation of Srx-1 expression. Nrf2-dependent Srx-1 expression was associated with the activation of p38 mitogen-activated protein kinases (MAPKs) in IECs. Furthermore, suppression of Srx-1 significantly enhanced apoptosis while overexpression of Srx-1 significantly attenuated apoptosis during exposure to BFT. These results imply that a signaling cascade involving p38 and Nrf2 is essential for Srx-1 upregulation in IECs stimulated with BFT. Following this upregulation, Srx-1 may control the apoptosis in BFT-exposed IECs.

scholarly journals Enterohemorrhagic Escherichia coli Infection Induces Interleukin-8 Production via Activation of Mitogen-Activated Protein Kinases and the Transcription Factors NF-κB and AP-1 in T84 Cells

2002 ◽  
Vol 70 (5) ◽  
pp. 2304-2310 ◽  
Author(s):  
Stephanie Dahan ◽  
Valere Busuttil ◽  
Veronique Imbert ◽  
Jean-Francois Peyron ◽  
Patrick Rampal ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Transcription Factors ◽  
Dna Binding ◽  
Protein Kinases ◽  
Binding Activity ◽  
Interleukin 8 ◽  
T84 Cells ◽  
Mitogen Activated Protein Kinases ◽  
Dna Binding Activity ◽  
Mitogen Activated Protein

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) infections are associated with hemorrhagic colitis and the hemolytic-uremic syndrome (HUS). In vivo, elevated plasma levels of the proinflammatory cytokine interleukin-8 (IL-8) in EHEC-infected children are correlated with a high risk of developing HUS. As IL-8 gene transcription is regulated by the transcription factors NF-κB and AP-1, we analyzed the role of these factors in the regulation of IL-8 production after infection of the epithelial intestinal T84 cell line by EHEC. By 6 h of infection, EHEC had induced significant secretion of IL-8 (35.84 ± 6.76 ng/ml versus 0.44 ± 0.04 ng/ml in control cells). EHEC induced AP-1 and NF-κB activation by 3 h of infection. Moreover, the three mitogen-activated protein kinases (MAPK) (ERK1/2, p38, and JNK) were phosphorylated in EHEC-infected T84 cells concomitant with induction of AP-1 DNA binding activity, and IκB-α was phosphorylated and then degraded concomitant with induction of NF-κB DNA binding activity. Pretreatment of cells with the highly specific MEK1/2 inhibitor U0126, the p38 inhibitor SB203580, and/or the proteasome inhibitor ALLN led to inhibition of the IL-8 secretion induced in EHEC-infected T84 cells. These findings demonstrate that (i) EHEC can induce in vitro a potent proinflammatory response by secretion of IL-8 and (ii) the secretion of IL-8 is due to the involvement of MAPK, AP-1, and NF-κB signaling pathways.

Influence of a High Salt Diet on Glomerular Injury and the Preventive Effects of Amiloride in Adriamycin Nephropathy

Nephron ◽  
1995 ◽  
Vol 71 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Akinori Nagashima ◽  
Seiya Okuda ◽  
Kiyoshi Tamaki ◽  
Masatoshi Fujishima
Keyword(s):  
High Salt ◽  
Glomerular Injury ◽  
High Salt Diet ◽  
Salt Diet ◽  
Adriamycin Nephropathy ◽  
Preventive Effects

Effects of diabetes and high-salt diet intake on the expression of mitochondrial protein kinases in rat heart

1994 ◽  
Vol 1 ◽  
pp. 438
Author(s):  
Y. Shimomura ◽  
N. Nakai ◽  
Y. Oshida ◽  
N. Fujitsuka ◽  
Y. Sato
Keyword(s):  
Protein Kinases ◽  
Rat Heart ◽  
Mitochondrial Protein ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Diet Intake

scholarly journals Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats

2018 ◽  
Vol 132 (11) ◽  
pp. 1179-1197 ◽  
Author(s):  
Sarah C. Ray ◽  
Bansari Patel ◽  
Debra L. Irsik ◽  
Jingping Sun ◽  
Hiram Ocasio ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Bicarbonate ◽  
Renal Injury ◽  
High Salt ◽  
Proton Channel ◽  
Pathological Feature ◽  
Glomerular Injury ◽  
High Salt Diet ◽  
Salt Diet ◽  
Inflammatory Status

Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.

PKCε modulates NF-κB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes

2000 ◽  
Vol 279 (4) ◽  
pp. H1679-H1689 ◽  
Author(s):  
Richard C. X. Li ◽  
Peipei Ping ◽  
Jun Zhang ◽  
William B. Wead ◽  
Xinan Cao ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Protein Kinases ◽  
Mapk Pathway ◽  
Binding Activity ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Adult Rabbit ◽  
Jnk Pathway ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

We have previously shown that protein kinase C (PKC)-ε, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) are essential signaling elements in ischemic preconditioning. In the present study, we examined whether activation of PKCε affects the activation of NF-κB in cardiac myocytes and whether MAPKs are mediators of this signaling event. Activation of PKCε (+108% above control) in adult rabbit cardiomyocytes to a degree that has been previously shown to protect myocytes against hypoxic injury increased the DNA-binding activity of NF-κB (+164%) and activator protein (AP)-1 (+127%) but not that of Elk-1. Activation of PKCη did not have an effect on these transcription factors. Activation of PKCε also enhanced the phosphorylation activities of the p44/p42 MAPKs and the p54/p46 c-Jun NH2-terminal kinases (JNKs). PKCε-induced activation of NF-κB and AP-1 was completely abolished by inhibition of the p44/p42 MAPK pathway with PD98059 and by inhibition of the p54/p46 JNK pathway with a dominant negative mutant of MAPK kinase-4, indicating that both signaling pathways are necessary. Taken together, these data identify NF-κB and AP-1 as downstream targets of PKCε, thereby establishing a molecular link between activation of PKCε and activation of NF-κB and AP-1 in cardiomyocytes. The results further demonstrate that both the p44/p42 MAPK and the p54/p46 JNK signaling pathways are essential mediators of this event.

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