| First Author | Thai TL | Year | 2012 |
| Journal | Am J Physiol Renal Physiol | Volume | 303 |
| Issue | 1 | Pages | F37-44 |
| PubMed ID | 22492943 | Mgi Jnum | J:187024 |
| Mgi Id | MGI:5435132 | Doi | 10.1152/ajprenal.00098.2012 |
| Citation | Thai TL, et al. (2012) Lack of protein kinase C-alpha leads to impaired urine concentrating ability and decreased aquaporin-2 in angiotensin II-induced hypertension. Am J Physiol Renal Physiol 303(1):F37-44 |
| abstractText | Regulation of water and urea transport in the inner medullary collecting duct is essential for urine concentration. Aquaporin (AQP)2 water channels and urea transporter (UT)-A1 are inserted into the apical membrane upon phosphorylation of the channels to allow the transcellular movement of water and urea. Since ANG II activates PKC in many cell types, we tested the hypothesis that ANG II-induced regulation of water and urea transport is mediated by PKC. Osmotic minipumps delivered ANG II to wild-type (WT) or PKC-alpha(-/-) mice for 7 days. Inner medullas were harvested, and protein abundance was determined by immunoblot. ANG II increased systolic blood pressure to a similar degree in WT and PKC-alpha(-/-) mice. ANG II had no effect on the urine output of WT mice but increased that of PKC-alpha(-/-) mice. In accordance with observed differences in urine output, AQP2 abundance was unchanged in ANG II-treated WT animals but was decreased in PKC-alpha(-/-) mice. No change in membrane accumulation was seen. Phosphorylation of the cAMP-induced transcription factor CREB was decreased in PKC-alpha(-/-) mice in response to ANG II with no change in overall CREB abundance. ANG II did not alter the abundance of UT-A1 protein in WT or PKC-alpha(-/-) mice. Phosphorylation and overall abundance of tonicity-responsive enhancer-binding protein, a transcription factor that regulates UT-A1, were also unaltered by ANG II in either group. We conclude that PKC-alpha protects against ANG II-induced decreases in urine concentrating ability by maintaining AQP2 levels through CREB phosphorylation. |
