| First Author | Mia S | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 476 |
| Issue | 4 | Pages | 267-272 |
| PubMed ID | 27230958 | Mgi Jnum | J:236046 |
| Mgi Id | MGI:5804500 | Doi | 10.1016/j.bbrc.2016.05.111 |
| Citation | Mia S, et al. (2016) Role of AMP-activated protein kinase alpha1 in angiotensin-II-induced renal Tgfss-activated kinase 1 activation. Biochem Biophys Res Commun 476(4):267-72 |
| abstractText | Angiotensin-II is a key factor in renal fibrosis. Obstructive nephropathy induces an isoform shift from catalytic Ampkalpha2 towards Ampkalpha1 which contributes to signaling involved in renal tissue injury. The present study explored whether the Ampkalpha1 isoform contributes to the renal effects of angiotensin-II. To this end, angiotensin-II was infused by subcutaneous implantation of osmotic minipumps in gene-targeted mice lacking functional Ampkalpha1 (Ampkalpha1(-/-)) and corresponding wild-type mice (Ampkalpha1(+/+)). Western blotting and qRT-PCR were employed to determine protein abundance and mRNA levels, respectively, in renal tissue. In Ampkalpha1(+/+) mice, angiotensin-II increased renal Ampkalpha1 protein expression without significantly modifying renal Ampkalpha2 protein expression. The renal phosphorylated Ampkalpha (Thr(172)) protein abundance was not affected by angiotensin-II in neither genotypes, but was significantly lower in Ampkalpha1(-/-) mice than Ampkalpha1(+/+) mice. Angiotensin-II increased the phosphorylation of Tak1 (Ser(412)) in renal tissue of Ampkalpha1(+/+) mice, an effect virtually absent in the Ampkalpha1(-/-) mice. Furthermore, angiotensin-II treatment significantly increased renal protein and mRNA expression of alpha-smooth muscle actin (alphaSma) as well as Tak1-target gene expression: Cox2, Il6 and Pai1 in Ampkalpha1(+/+) mice, all effects significantly less pronounced in Ampkalpha1(-/-) mice. In conclusion, angiotensin-II up-regulates the Ampkalpha1 isoform in renal tissue. Ampkalpha1 participates in renal Tak1 activation and Tak1-dependent signaling induced by angiotensin-II. |
