H2O2 and Src-dependent transactivation of the EGF receptor mediates the stimulatory effect of leptin on renal ERK and Na+, K+-ATPase

Bełtowski, Jerzy; Wójcicka, Grażyna; Trzeciak, Jadwiga; Marciniak, Andrzej

doi:10.1016/j.peptides.2006.08.010

Cited by 23 publications

(22 citation statements)

References 57 publications

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“…the brain, liver, adipose tissue, and skeletal muscles) (41). Leptin stimulates Hck in isolated human neutrophils and c-Src in rat kidney (42,43). We demonstrated that overexpressed c-Src was constitutively active and tyrosyl-phosphorylated STAT3.…”

Section: Discussionmentioning

confidence: 81%

Leptin Stimulates Both JAK2-dependent and JAK2-independent Signaling Pathways

Jiang

Rui

2008

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 81%

Leptin Stimulates Both JAK2-dependent and JAK2-independent Signaling Pathways

Jiang

Rui

2008

Journal of Biological Chemistry

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“…First, the electrical driving force (the membrane potential) may be elevated because H 2 O 2 stimulates both K ATP channels (13) and large conductance, calcium-and voltage-activated potassium (BK) channels (37). Second, the chemical driving force (Na ϩ concentration gradient) may also be elevated because H 2 O 2 also stimulates Na ϩ ,K ϩ -ATPase (38), which could decrease intracellular Na ϩ . Investigation of the underlying mechanism will be the direction of our future studies.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Peroxide Stimulates the Epithelial Sodium Channel through a Phosphatidylinositide 3-Kinase-dependent Pathway

2011

Journal of Biological Chemistry

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ENaC 2 in the distal nephron plays an important role in maintaining Na ϩ homeostasis and consequently controls systemic blood pressure. Excess sodium reabsorption due to enhanced ENaC activity can lead to hypertension, as is seen in Liddle syndrome (1, 2) and other genetic diseases (3). Surprisingly, whether high salt intake induces hypertension by targeting ENaC has not been examined. High salt intake can elevate both superoxide (O 2 . ) (4, 5) and H 2 O 2 (6) in the kidney by stimulating NAD(P)H oxidase (7-9), and O 2 . can increase aldosterone-me- , stimulate the non-receptor tyrosine kinase, c-Src (15). c-Src is known to be directly associated with p85, the regulatory subunit of PI3K (16). Tyrosine phosphorylation of p85 reduces its inhibitory effect on PI3K (17). These studies indicate that ROS may stimulate PI3K and consequently promote the synthesis of PI(3,4,5)P 3 . We (18 -20) and others (21,22) have previously shown that PI(3,4,5)P 3 stimulates ENaC. Taken together, these studies suggest that H 2 O 2 may stimulate ENaC by elevating PI(3,4,5)P 3 through activation of PI3K. In the present study, using patch clamp techniques combined with confocal microscopy analysis of apical PI(3,4,5)P 3 levels, we show that H 2 O 2 stimulates ENaC in A6 distal nephron cells via PI3K-dependent elevation of PI(3,4,5)P 3 in the apical membrane. MATERIALS AND METHODSCell Culture-Xenopus A6 distal nephron cells were purchased from the American Type Culture Collection (Manassas, VA). Under previously used culture conditions, basal activity of ENaC in A6 cells is relatively high (23). It is difficult to see and analyze any stimulatory effect when basal ENaC activity is high. Therefore, in the present study, we modified the culture medium to reduce basal ENaC activity. The medium contained 2 parts of DMEM/F-12 (1:1) medium (Invitrogen), 1 part of H 2 O, 15 mM NaHCO 3 (total Na ϩ ϭ 101 mM, which is ideal for amphibian A6 cells), 2 mM L-glutamine, 10% fetal bovine serum (Invitrogen), 25 units/ml penicillin, 25 units/ml streptomycin. A6 cells were cultured in plastic flasks in the presence of 1 M aldosterone at 26°C and 4% CO 2 . After the cells became 70% * This work was supported, in whole or in part, by National Institutes of Health Grant 5R01-DK067110 (to H.-P. M.

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“…Phospho-ERK and total ERK concentrations were measured by enzyme immunoassay (EIA) using kits obtained from Assay Designs, Inc. (Ann Arbor, MI, USA) as previously described (Bełtowski et al, 2006).…”

Section: Erk Phosphorylation Assaymentioning

confidence: 99%