Vasopressin at Central Levels and Consequences of Dehydration

Bichet, Daniel G.

doi:10.1159/000446200

Cited by 13 publications

(20 citation statements)

References 14 publications

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“…During dehydration and hypernatremia, AVP is secreted by the pituitary gland and binds type-2 receptor (V2R) at the basolateral membrane of renal collecting duct principal cells [1-4]. Activation of the cAMP/PKA signal transduction pathway stimulates the translocation of AQP2-bearing vesicles to the apical plasma membrane increasing luminal permeability [5-7].…”

Section: Introductionmentioning

confidence: 99%

AQP2 Abundance is Regulated by the E3-Ligase CHIP Via HSP70

Centrone

Ranieri

Mise

et al. 2017

Cell Physiol Biochem

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Background/Aims: AQP2 expression is mainly controlled by vasopressin-dependent changes in protein abundance which is in turn regulated by AQP2 ubiquitylation and degradation, however the proteins involved in these processes are largely unknown. Here, we investigated the potential role of the CHIP E3 ligase in AQP2 regulation. Methods: MCD4 cells and kidney slices were used to study the involvement of the E3 ligase CHIP on AQP2 protein abundance by cell homogenization and immunoprecipitation followed by immunoblotting. Results: We found that AQP2 complexes with CHIP in renal tissue. Expression of CHIP increased proteasomal degradation of AQP2 and HSP70 abundance, a molecular signature of HSP90 inhibition. Increased HSP70 level, secondary to CHIP expression, promoted ERK signaling resulting in increased AQP2 phosphorylation at S261. Phosphorylation of AQP2 at S256 and T269 were instead downregulated. Next, we investigated HSP70 interaction with AQP2, which is important for endocytosis. Compared with AQP2-wt, HSP70 binding decreased in AQP2-S256D and AQP2-S256D-S261D, while increased in AQP2-S256D-S261A. Surprisingly, expression of CHIP-delUbox, displaying a loss of E3 ligase activity, still induced AQP2 degradation, indicating that CHIP does not ubiquitylate and degrade AQP2 itself. Conversely, the AQP2 half-life was increased upon the expression of CHIP-delTPR a domain which binds Hsc70/HSP70 and HSP90. HSP70 has been reported to bind other E3 ligases such as MDM2. Notably, we found that co-expression of CHIP and MDM2 increased AQP2 degradation, whereas co-expression of CHIP with MDM2-delRING, an inactive form of MDM2, impaired AQP2 degradation. Conclusion: Our findings indicate CHIP as a master regulator of AQP2 degradation via HSP70 that has dual functions: (1) as chaperone for AQP2 and (2) as an anchoring protein for MDM2 E3 ligase, which is likely to be involved in AQP2 degradation.

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Section: Introductionmentioning

confidence: 99%

AQP2 Abundance is Regulated by the E3-Ligase CHIP Via HSP70

Centrone

Ranieri

Mise

et al. 2017

Cell Physiol Biochem

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“…During dehydration, the brain coordinates a behavioural (thirst) and physiological response that serve to buffer increased extracellular fluid osmolality and decreased intravascular volume. The physiological response consists of 2 principle effectors: AVP and the sympathetic nervous system, which together enhance renal water reabsorption, in defence of extracellular fluid osmolality, and increase vascular tone, to support arterial blood pressure [23].…”

Section: Central Osmoreception and Blood Pressure Controlmentioning

confidence: 99%

“…The forebrain lamina terminalis is responsible for detecting plasma osmolality and initiating the behavioural and physiological response [23]. Plasma tonicity (i.e., plasma osmolality without membrane permeable solutes) is transduced by specialised osmoreceptor neurons located in 2 circumventricular organs of the lamina terminals: the organum vasculosum of the lamina terminalis (OVLT) and the subfornical organ (SFO).…”

Section: Central Osmoreception and Blood Pressure Controlmentioning

confidence: 99%

“…These neuronal pathways are robustly activated during dehydration [24]. The PVN and SON contain magnocellular neurosecretory neurons that release AVP into the peripheral circulation, while the PVN harbors an additional population of neurons that generate vasomotor and renal sympathetic outflow [23] (Fig. 2).…”

Section: Central Osmoreception and Blood Pressure Controlmentioning

confidence: 99%

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Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension

Underwood¹,

Phillips²,

Hildreth³

2018

Ann Nutr Metab

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Polycystic kidney disease (PKD) is a group of monogenetic conditions characterised by the progressive accumulation of multiple renal cysts and hypertension. One of the earliest features of PKD is a reduction in urinary concentrating capacity that impairs extracellular fluid conservation. Urinary concentrating impairment predisposes PKD patients to periods of hypohydration when fluid loss is not adequately compensated by fluid intake. The hypohydrated state provides a blood hyperosmotic stimulus for vasopressin release to minimise further water loss. However, over-activation of renal V₂ receptors contributes to cyst expansion. Although suppressing vasopressin release with high water intake has been shown to impair disease progression in rodent models, whether this approach is efficacious in patients remains uncertain. The neural osmoregulatory pathway that controls vasopressin secretion also exerts a stimulatory action on vasomotor sympathetic activity and blood pressure during dehydration. Recurrent dehydration leads to a worsening of hypertension in rodents and cross-sectional data suggests that reduced urinary concentrating ability may contribute to hypertension development in the clinical PKD population. Experimental studies are required to evaluate this hypothesis and to determine the underlying mechanism.

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“…Daniel Bichet, PhD, University of Montreal, Canada described an essential component of body water balance in his article, "Vasopressin and the regulation of thirst." His topic expanded a previous publication in this journal [1]. Professor Bichet began by explaining 2 ways in which the brain perceives dehydration: increased blood concentration and decreased pressure within blood vessels.…”

mentioning

confidence: 98%

Hydration for Health Conference Emphasizes Vasopressin and Kidney Diseases

Armstrong¹

2018

Ann Nutr Metab

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Vasopressin at Central Levels and Consequences of Dehydration

Cited by 13 publications

References 14 publications

AQP2 Abundance is Regulated by the E3-Ligase CHIP Via HSP70

AQP2 Abundance is Regulated by the E3-Ligase CHIP Via HSP70

Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension

Hydration for Health Conference Emphasizes Vasopressin and Kidney Diseases

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