Arachidonic acid mediates angiotensin II effects on p21ras in renal proximal tubular cells via the tyrosine kinase-Shc-Grb2-Sos pathway

Jiao, Huaiyuan; Cui, Xiaolan; Torti, Mauro; Chang, Chung-Ho; Alexander, Larry D.; Lapetina, Eduardo G.; Douglas, Janice G.

doi:10.1073/pnas.95.13.7417

Cited by 41 publications

(29 citation statements)

References 26 publications

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“…A very similar result was obtained in the presence of pyrrophenone (data not shown). Contrary to the proposal by Douglas and colleagues, [11][12][13][14] these results indicate that the cPLA 2 /P450 pathway actually works to suppress the AT 1 -mediated ERK activation in intact proximal tubules.…”

Section: Role Of Cpla 2 In Wild-type Micecontrasting

confidence: 56%

“…Arachidonic acid, in turn, either through cytochrome P450 metabolites or directly, stimulates the ERK pathway. [11][12][13][14][15][16] In sharp contrast to their proposal, however, several studies suggested that Ang II type 1 receptor (AT 1 ) mediates both stimulatory and inhibitory effects of Ang II. 10,17 Our own data obtained from AT 1A -deficient mice also led us to conclude that AT 1 mediates the biphasic regulation in intact mouse proximal tubules.…”

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confidence: 99%

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Roles of ERK and cPLA2 in the Angiotensin II-Mediated Biphasic Regulation of Na+-HCO3 − Transport

Li¹,

Yamada²,

Kita

et al. 2008

Journal of the American Society of Nephrology

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Regulation of renal proximal transport by angiotensin II (Ang II) is biphasic: low concentrations (picomolar to nanomolar) stimulate reabsorption, but higher concentrations (nanomolar to micromolar) inhibit reabsorption. Traditionally, the stimulatory effect has been attributed to activation of protein kinase C and/or a decrease in intracellular cAMP, whereas the inhibitory action has been attributed to the activation of phospholipase A 2 (PLA 2 ) and the subsequent release of arachidonic acid. The Ang II receptor subtype responsible for these effects and the intracellular signaling pathways involved are not completely understood. We isolated proximal tubules from wild-type, Ang II type 1A receptor (AT 1A )-deficient, and group IVA cytosolic phospholipase A 2 (cPLA 2 ␣)-deficient mice, and compared their responses to Ang II. In wild-type mice, we found that the stimulatory and inhibitory effects of Ang II on Na ϩ -HCO 3 Ϫ cotransporter activity are both AT 1 -mediated but that ERK activation only plays a role in the former. The stimulatory effect of Ang II was also observed in AT 1A -deficient mice, suggesting that this occurs through AT 1B . In contrast, the inhibitory effects of Ang II appeared to be mediated by cPLA 2 ␣ activation because high-concentration Ang II stimulated Na ϩ -HCO 3 Ϫ cotransporter activity when cPLA 2 ␣ activity was abrogated by pharmacological means or genetic knockout. Consistent with this observation, we found that activation of the cPLA 2 ␣/P450 pathway suppressed ERK activation. We conclude that Ang II activates ERK and cPLA 2 ␣ in a concentration-dependent manner via AT 1 , and that the balance between ERK and cPLA 2 ␣ activities determines the ultimate response to Ang II in intact proximal tubules.

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Section: Role Of Cpla 2 In Wild-type Micecontrasting

confidence: 56%

mentioning

confidence: 99%

Roles of ERK and cPLA2 in the Angiotensin II-Mediated Biphasic Regulation of Na+-HCO3 − Transport

Li¹,

Yamada²,

Kita

et al. 2008

Journal of the American Society of Nephrology

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“…We have previously demonstrated that arachidonic acid mimics Ang II in activation of Src tyrosine kinase, induction of Src and EGFR association via SH2 domain, transactivation of the EGFR tyrosine kinase, activation of small GTPase ras, and activation of downstream ERK1/2 [11,12,14,22]. Experiments were designed to test whether Src and EGFR tyrosine kinases are responsible for mediating H 2 O 2 -induced signaling in these epithelial cells.…”

Section: Resultsmentioning

confidence: 99%

“…Transactivation of the EGFR tyrosine kinase is an upstream element of shc/grb2/sos-mediated ras activation in our system [11,12]. Recently, we have demonstrated that arachidonic acid and/or its metabolites mediate all downstream effects of Ang II in activation of members of the MAPK, i.e., the ERK1/2, p46/p54 SAPK , and p38 SAPK [13,14].…”

Section: Introductionmentioning

confidence: 99%

Oxidative signaling in renal epithelium: Critical role of cytosolic phospholipase A2 and p38SAPK

Cui

Ding

Alexander

et al. 2006

Free Radical Biology and Medicine

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Previous studies from this laboratory have demonstrated a critical role of cytosolic phospholipase A 2 (cPLA 2 ) and arachidonic acid in angiotensin II (Ang II) AT2 receptor-mediated signal transduction in renal epithelium. In primary proximal tubular epithelial cells exposed to hydrogen peroxide (H 2 O 2 ), both the selective cPLA 2 inhibitors and the cPLA 2 antisense oligonucleotides significantly attenuated H 2 O 2 -induced arachidonic acid liberation and activation of p38 SAPK , ERK1/2, and Akt1. This H 2 O 2 -induced kinase activation was significantly attenuated by a Src kinase inhibitor PP2, or by transient transfection of carboxyl-terminal Src kinase (CSK) that maintained Src in the dormant form. Under basal conditions, Src coimmunoprecipitated with epidermal growth factor receptor (EGFR), while H 2 O 2 increased EGFR phosphorylation in the complex. We observed that inhibition of EGFR kinase activity with AG1478 significantly attenuated H 2 O 2 -induced p38 SAPK and ERK1/2 activation, but did not inhibit Akt1 activation. Furthermore, it seems that p38 SAPK is upstream of ERK1/2 and Akt1, since a p38 SAPK inhibitor SB203580 significantly blocked H 2 O 2 -induced activation of ERK1/2 and Akt1. Interestingly, overexpression of the dominant-negative p38 SAPK isoform α inhibited ERK1/2 but not Akt1 activation. Our observations demonstrate that in these nontransformed cells, activation of cPLA 2 is a converging point for oxidative stress and Ang II, which share common downstream signaling mechanisms including Src and EGFR. In addition, p38 SAPK provides a positive input to both growth and antiapoptotic signaling pathways induced by acute oxidative stress.

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“…Additional studies form this laboratory have documented that cPLA 2 -mediated signaling is linked to the relatively low-affinity AT 2 ANG II receptor (3,19,25,26) that is pharmacologically distinct from the AT 2 receptor cloned previously (22,36). Moreover, this apical AT 2 receptor mediates ANG II-induced arachidonic acid release and downstream events such as Shc/Grb2/Sos and p21 ras association, and c-Src and ERK1/2 activation (3,12,25,26). Thus this represents an additional signaling model for AT 2 receptor subtypes and G protein-coupled receptors as well.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II stimulates fibronectin protein synthesis via a Gβγ/arachidonic acid-dependent pathway

Alexander

Ding

Alagarsamy

et al. 2014

American Journal of Physiology-Renal Physiology

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Alexander LD, Ding Y, Alagarsamy S, Cui X. Angiotensin II stimulates fibronectin protein synthesis via a G␤␥/arachidonic aciddependent pathway. Am J Physiol Renal Physiol 307: F287-F302, 2014. First published June 11, 2014 doi:10.1152/ajprenal.00094.2014.-In rabbit proximal tubular cells, ANG II type 2-receptor (AT 2 )-induced arachidonic acid release is PLA 2 coupled and dependent of G protein ␤␥ (G␤␥) subunits. Moreover, ANG II activates ERK1/2 and transactivates EGFR via a c-Src-dependent mechanism. Arachidonic acid has been shown to mimic this effect, at least in part, by an undetermined mechanism. In this study, we determined the effects of ANG II on fibronectin expression in cultured rabbit proximal tubule cells and elucidated the signaling pathways associated with such expression. We found that ANG II and transfection of G␤␥ subunits directly increased fibronectin protein expression, and this increase was inhibited by overexpression of ␤-adrenergic receptor kinase (␤ARK)-ct or DN-Src. Moreover, ANG II-induced fibronectin protein expression was significantly abrogated by the AT2 receptor antagonist PD123319. In addition, inhibition of cystolic PLA 2 diminished ANG II-induced fibronectin expression. Endogenous arachidonic acid mimicked ANG II-induced fibronectin expression. We also found that overexpression of G␤␥ subunits induced c-Src, ERK1/2, and EGFR tyrosine phosphorylation, which can be inhibited by overexpression of ␤ARK-ct or DN-Src. G␤␥ also induced c-Src SH2 domain association with the EGFR. Supporting these findings, in rabbit proximal tubular epithelium, immunoblot analysis indicated that ␤␥ expression was significant. Interestingly, arachidonic acid-and eicosatetraenoic acid-induced responses were preserved in the presence of ␤ARK-ct. This is the first report demonstrating the regulation of EGFR, ERK1/2, c-Src, and fibronectin by G␤␥ subunits in renal epithelial cells. Moreover, this work demonstrates a role for G␤␥ heterotrimeric proteins in ANG II, but not arachidonic acid, signaling in renal epithelial cells. arachidonic acid; angiotensin II; c-Src, epidermal growth factor receptor transactivation; carboxyl terminus of ␤-adrenergic receptor kinase-1; mitogen-activated protein kinase; G␤␥

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Arachidonic acid mediates angiotensin II effects on p21ras in renal proximal tubular cells via the tyrosine kinase-Shc-Grb2-Sos pathway

Cited by 41 publications

References 26 publications

Roles of ERK and cPLA2 in the Angiotensin II-Mediated Biphasic Regulation of Na+-HCO3 − Transport

Roles of ERK and cPLA2 in the Angiotensin II-Mediated Biphasic Regulation of Na+-HCO3 − Transport

Oxidative signaling in renal epithelium: Critical role of cytosolic phospholipase A2 and p38SAPK

Angiotensin II stimulates fibronectin protein synthesis via a Gβγ/arachidonic acid-dependent pathway

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