PMID:18367658

Citation	Combet, S, Gouraud, S, Gobin, R, Berthonaud, V, Geelen, G, Corman, B and Verbavatz, JM (2008) Aquaporin-2 downregulation in kidney medulla of aging rats is posttranscriptional and is abolished by water deprivation. Am. J. Physiol. Renal Physiol. 294:F1408-14
Abstract	Aging kidney is associated in humans and rodents with polyuria and reduced urine concentrating ability. In senescent female WAG/Rij rats, this defect is independent of arginine-vasopressin (AVP)/V(2) receptor/cAMP pathway. It has been attributed to underexpression and mistargeting of aquaporin-2 (AQP2) water channel in the inner medullary collecting duct (IMCD). We showed previously that dDAVP administration could partially correct this defect. Since AQP2 can also be regulated by AVP-independent pathways in water deprivation (WD), we investigated AQP2 and phosphorylated AQP2 (p-AQP2) regulation in thirsted adult (10 mo old) and senescent (30 mo old) female WAG/Rij rats. Following 2-day WD, urine flow rate decreased and urine osmolality increased in both groups. However, in agreement with significantly lower cortico-papillary osmotic gradient with aging, urine osmolality remained lower in senescent animals. WD induced sixfold increase of plasma AVP in all animals which, interestingly, did not result in higher papillary cAMP level. Following WD, AQP2 and p-AQP2 expression increased hugely in 10- and 30-mo-old rats and their mistargeting in old animals was corrected. Moreover, the age-related difference in AQP2 regulation was abolished after WD. To further investigate the mechanism of AQP2 underexpression with aging, AQP2 mRNA was quantified by real-time RT-PCR. In the outer medulla, preservation of AQP2 protein expression was achieved through increased AQP2 mRNA level in senescent rats. In the IMCD, no change in AQP2 mRNA was detected with aging but AQP2 protein expression was markedly lower in 30-mo-old animals. In conclusion, there is a posttranscriptional downregulation of AQP2 with aging, which is abolished by WD.
Links	PubMed Online version:10.1152/ajprenal.00437.2007
Keywords	Aging/physiology; Animals; Aquaporin 2/genetics; Aquaporin 2/metabolism; Cyclic AMP/metabolism; Cyclic GMP/metabolism; Down-Regulation/physiology; Female; Kidney Concentrating Ability/physiology; Kidney Medulla/physiology; Osmolar Concentration; Phosphorylation; RNA Processing, Post-Transcriptional/physiology; RNA, Messenger/metabolism; Rats; Rats, Inbred Strains; Reverse Transcriptase Polymerase Chain Reaction; Water Deprivation/physiology; Water-Electrolyte Balance/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:AQP2	involved_in	GO:0009414: response to water deprivation	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete
RAT:AQP2	involved_in	GO:0007568: aging	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

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