KEGG   PATHWAY: ko04960Help
Entry
ko04960                     Pathway                                

Name
Aldosterone-regulated sodium reabsorption
Description
Sodium transport across the tight epithelia of Na+ reabsorbing tissues such as the distal part of the kidney nephron and colon is the major factor determining total-body Na+ levels, and thus, long-term blood pressure. Aldosterone plays a major role in sodium and potassium metabolism by binding to epithelial mineralocorticoid receptors (MR) in the renal collecting duct cells localized in the distal nephron, promoting sodium resorption and potassium excretion. Aldosterone enters a target cell and binds MR, which translocates into the nucleus and regulates gene transcription. Activation of MR leads to increased expression of Sgk-1, which phosphorylates Nedd4-2, an ubiquitin-ligase which targets ENAC to proteosomal degradation. Phosphorylated Nedd4-2 dissociates from ENAC, increasing its apical membrane abundance. Activation of MR also leads to increased expression of Na+/K+-ATPase, thus causing a net increase in sodium uptake from the renal filtrate. The specificity of MR for aldosterone is provided by 11beta-HSD2 by the rapid conversion of cortisol to cortisone in renal cortical collecting duct cells. Recently, besides genomic effects mediated by activated MR, rapid aldosterone actions that are independent of translation and transcription have been documented.
Class
Organismal Systems; Excretory system
BRITE hierarchy
Pathway map
ko04960  Aldosterone-regulated sodium reabsorption
ko04960

Ortholog table
Disease
H00239  Bartter syndrome
H00242  Liddle syndrome
H00243  Hyperkalemic distal renal tubular acidosis (RTA type 4)
H00603  Hypertension exacerbated in pregnancy
H00719  Leprechaunism
H00892  Bronchiectasis with or without elevated sweat chloride
H00942  Rabson-Mendenhall syndrome
H00998  Alternating hemiplegia of childhood
H01228  Insulin-resistant diabetes mellitus with acanthosis nigricans (IRAN)
H01603  Primary aldosteronism
Orthology
K00071  corticosteroid 11-beta-dehydrogenase isozyme 2 [EC:1.1.1.-]
K08555  mineralocorticoid receptor
K04824  amiloride-sensitive sodium channel subunit alpha
K04825  amiloride-sensitive sodium channel subunit beta
K04827  amiloride-sensitive sodium channel subunit gamma
K13302  serum/glucocorticoid-regulated kinase 1 [EC:2.7.11.1]
K04995  potassium inwardly-rectifying channel subfamily J member 1
K13358  Na(+)/H(+) exchange regulatory cofactor NHE-RF2
K13305  E3 ubiquitin-protein ligase NEDD4-like [EC:2.3.2.26]
K06644  stratifin
K07827  GTPase KRas
K01539  sodium/potassium-transporting ATPase subunit alpha [EC:3.6.3.9]
K01540  sodium/potassium-transporting ATPase subunit beta
K01538  sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K13359  FXYD domain containing ion transport regulator 4
K04526  insulin
K05459  insulin-like growth factor 1
K04527  insulin receptor [EC:2.7.10.1]
K16172  insulin receptor substrate 1
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K06276  3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
Compound
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C00698  Cl-
C00735  Cortisol
C00762  Cortisone
C01330  Sodium cation
C01780  Aldosterone
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Connell JM, Davies E
  Title
The new biology of aldosterone.
  Journal
J Endocrinol 186:1-20 (2005)
DOI:10.1677/joe.1.06017
Reference
  Authors
Booth RE, Johnson JP, Stockand JD
  Title
Aldosterone.
  Journal
Adv Physiol Educ 26:8-20 (2002)
DOI:10.1152/advan.00123.2015
Reference
  Authors
Lee IH, Campbell CR, Cook DI, Dinudom A
  Title
Regulation of epithelial Na+ channels by aldosterone: role of Sgk1.
  Journal
Clin Exp Pharmacol Physiol 35:235-41 (2008)
DOI:10.1111/j.1440-1681.2007.04844.x
Reference
  Authors
Viengchareun S, Le Menuet D, Martinerie L, Munier M, Pascual-Le Tallec L, Lombes M
  Title
The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology.
  Journal
Nucl Recept Signal 5:e012 (2007)
DOI:10.1621/nrs.05012
Reference
  Authors
Fuller PJ, Young MJ
  Title
Mechanisms of mineralocorticoid action.
  Journal
Hypertension 46:1227-35 (2005)
DOI:10.1161/01.HYP.0000193502.77417.17
Reference
  Authors
Verrey F, Loffing J, Zecevic M, Heitzmann D, Staub O
  Title
SGK1: aldosterone-induced relay of Na+ transport regulation in distal kidney nephron cells.
  Journal
Cell Physiol Biochem 13:21-8 (2003)
DOI:10.1159/000070246
Reference
  Authors
Pearce D, Kleyman TR
  Title
Salt, sodium channels, and SGK1.
  Journal
J Clin Invest 117:592-5 (2007)
DOI:10.1172/JCI31538
Reference
  Authors
Grossmann C, Gekle M
  Title
New aspects of rapid aldosterone signaling.
  Journal
Mol Cell Endocrinol 308:53-62 (2009)
DOI:10.1016/j.mce.2009.02.005
Reference
  Authors
Vallon V, Wulff P, Huang DY, Loffing J, Volkl H, Kuhl D, Lang F
  Title
Role of Sgk1 in salt and potassium homeostasis.
  Journal
Am J Physiol Regul Integr Comp Physiol 288:R4-10 (2005)
DOI:10.1152/ajpregu.00369.2004
Reference
  Authors
Rogerson FM, Brennan FE, Fuller PJ
  Title
Dissecting mineralocorticoid receptor structure and function.
  Journal
J Steroid Biochem Mol Biol 85:389-96 (2003)
DOI:10.1016/S0960-0760(03)00200-0
Reference
  Authors
Wang J, Barbry P, Maiyar AC, Rozansky DJ, Bhargava A, Leong M, Firestone GL, Pearce D
  Title
SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport.
  Journal
Am J Physiol Renal Physiol 280:F303-13 (2001)
Reference
  Authors
Good DW
  Title
Nongenomic actions of aldosterone on the renal tubule.
  Journal
Hypertension 49:728-39 (2007)
DOI:10.1161/01.HYP.0000259797.48382.b2

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