Noradrenaline enhances angiotensin II responses via p38 MAPK activation after hypoxia/re‐oxygenation in renal interlobar arteries

Kaufmann, Jan; Martinka, Peter; Moede, Olivia; Sendeski, Mauricio; Steege, Andreas; Fähling, Michael; Hultström, Michael; Gaestel, Matthias; Moraes‐Silva, Ivana C.; Nikitina, Tatiana; Liu, Z. Z.; Zavaritskaya, Olga; Patzak, Andreas

doi:10.1111/apha.12457

Cited by 16 publications

(21 citation statements)

References 38 publications

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“…Hypoxia in combination with noradrenaline enhances the vasoreactivity of renal arteries after hypoxia/reoxygenation by activating p38 MAPK in mouse model, which was suggested to be essential for the pathogenesis of AKI [12]. Recent studies on rabbits in New Zealand showed that increasing the expression of aldehyde dehydrogenase 2 can reduce renal cell apoptosis by inhibiting the p38 and JNK pathways in rabbits with I/R injury [66].…”

Section: Other Mapksmentioning

confidence: 99%

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Luo

Shi

et al. 2016

Cell Physiol Biochem

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Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis. However, the underlying signaling mechanisms, whereby hypoxia alters cellular behaviors, remain poorly understood. Mitogen-activated protein kinases (MAPKs) are key signal-transducing enzymes activated by a wide range of extracellular stimuli, including hypoxia/ischemia. There are four major family members of MAPKs: the extracellular signal-regulated kinases-1 and -2 (ERK1/2), the c-Jun N-terminal kinases (JNK), p38 MAPKs, and extracellular signal-regulated kinase-5 (ERK5/BMK1). Recent studies, including ours, suggest that these MAPKs are differentially involved in renal responses to hypoxic/ischemic stress. This review will discuss their changes in hypoxic/ischemic pathophysiology with acute kidney injury, chronic kidney diseases and renal carcinoma.

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Section: Other Mapksmentioning

confidence: 99%

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Luo

Shi

et al. 2016

Cell Physiol Biochem

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“…However, its expression and possible physiologic role in the kidney remains to be fully clarified. There are indications in mice that β 3 -AR mRNA is expressed by renal arteries 16 . In addition, in the rat kidney, a cDNA microarray screening showed that β 3 -AR is expressed in the kidney medulla 17 .…”

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confidence: 99%

“…In addition, in the rat kidney, a cDNA microarray screening showed that β 3 -AR is expressed in the kidney medulla 17 . Moreover, in humans, β 3 -AR polymorphisms seem to be associated with the effect of thiazide diuretics,16, 18 suggesting a role for β 3 -AR in regulating renal water reabsorption. In this respect, demonstrating this novel role of β 3 -AR in renal physiology is particularly intriguing in light of potential therapeutic applications of β 3 -AR–acting drugs in diseases characterized by altered diuresis.…”

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confidence: 99%

β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function

Procino

Carmosino

Milano

et al. 2016

Kidney International

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To date, the study of the sympathetic regulation of renal function has been restricted to the important contribution of β1- and β2-adrenergic receptors (ARs). Here we investigate the expression and the possible physiologic role of β3-adrenergic receptor (β3-AR) in mouse kidney. The β3-AR is expressed in most of the nephron segments that also express the type 2 vasopressin receptor (AVPR2), including the thick ascending limb and the cortical and outer medullary collecting duct. Ex vivo experiments in mouse kidney tubules showed that β3-AR stimulation with the selective agonist BRL37344 increased intracellular cAMP levels and promoted 2 key processes in the urine concentrating mechanism. These are accumulation of the water channel aquaporin 2 at the apical plasma membrane in the collecting duct and activation of the Na-K-2Cl symporter in the thick ascending limb. Both effects were prevented by the β3-AR antagonist L748,337 or by the protein kinase A inhibitor H89. Interestingly, genetic inactivation of β3-AR in mice was associated with significantly increased urine excretion of water, sodium, potassium, and chloride. Stimulation of β3-AR significantly reduced urine excretion of water and the same electrolytes. Moreover, BRL37344 promoted a potent antidiuretic effect in AVPR2-null mice. Thus, our findings are of potential physiologic importance as they uncover the antidiuretic effect of β3-AR stimulation in the kidney. Hence, β3-AR agonism might be useful to bypass AVPR2-inactivating mutations.

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“…43 Indeed, MAPKs have been implicated as an important regulator for cell survival/injury under hypoxic conditions. 44,45 Among them, the role of ERK1/2 has been considered a protective factor for cell survival, while p38 is considered a factor for cell injury. 20,[46][47][48][49] In cultured rat cortical neurons, hypoxia differentially regulated the phosphorylation of p38 and ERK1/2, 27 whereas in the rat hippocampal slices, the phosphorylation of both p38 and ERK2, but not ERK1, was upregulated in response to hypoxia.…”

Section: Discussionmentioning

confidence: 99%

ERK and p38 upregulation versus Bcl-6 downregulation in rat kidney epithelial cells exposed to prolonged hypoxia

Luo

Shi

et al. 2017

cell transplant

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Hypoxia is a common cause of kidney injury and a major issue in kidney transplantation. Mitogen-activated protein kinases (MAPKs) are involved in the cellular response to hypoxia, but the precise roles of MAPKs in renal cell reactions to hypoxic stress are not well known yet. This work was conducted to investigate the regulation of extracellular signal-regulated kinase-1 and -2 (ERK1/2) and p38 and their signaling-relevant molecules in kidney epithelial cells exposed to prolonged hypoxia. Rat kidney epithelial cells Normal Rat Kidney (NRK)-52E were exposed to hypoxic conditions (1% O 2 ) for 24 to 72 h. Cell morphology was examined by light microscopy, and cell viability was checked by 3-The expression of ERK1/2 and p38 MAPK, as well as their signaling-related molecules, was measured by Western blot and real-time polymerase chain (RT-PCR) reaction. At the 1% oxygen level, cell morphology had no appreciable changes compared to the control up to 72 h of exposure under light microscopy, whereas the results of MTS showed a slight but significant reduction in cell viability after 72 h of hypoxia. On the other hand, ERK1/2 and p38 phosphorylation remarkably increased in these cells after 24 to 72 h of hypoxia. In sharp contrast, the expression of transcription factor B-cell lymphoma 6 (Bcl-6) was significantly downregulated in response to hypoxic stress. Other intracellular molecules relevant to the ERK1/2 and p38 signaling pathway, such as protein kinase A, protein kinase C, Bcl-2, nuclear factor erythroid 2-related factor 2, tristetraprolin, and interleukin-10(IL-10), had no significant alterations after 24 to 72 h of hypoxic exposure. We conclude that hypoxic stress increases the phosphorylation of both ERK1/2 and p38 but decreases the level of Bcl-6 in rat kidney epithelial cells.

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Noradrenaline enhances angiotensin II responses via p38 MAPK activation after hypoxia/re‐oxygenation in renal interlobar arteries

Abstract: The results suggest an interaction of NE and hypoxia in enhancing vasoreactivity, which may be important for the pathogenesis of AKI. The effect of NE+hypoxia in ILA is mediated by several adrenergic receptors and requires the p38 MAPK activation.

Cited by 16 publications

References 38 publications

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function

ERK and p38 upregulation versus Bcl-6 downregulation in rat kidney epithelial cells exposed to prolonged hypoxia

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