Upregulation of cAMP is a new functional signal pathway of Klotho in endothelial cells

作者：Yang J; Matsukawa N; Rakugi H^*; Imai M; Kida I; Nagai M; Ohta J; Fukuo K; Nabeshima Y; Ogihara T

来源：Biochemical and Biophysical Research Communications, 2003, 301(2): 424-429.

DOI：10.1016/S0006-291X(02)03056-5

• Klotho
• angiotensin 1-converting enzyme
• cAMP
• endothelial cell

We measured angiotensin I-converting enzyme (ACE) activity in a human endothelial cell to characterize the intracellular signal pathways of Klotho. COS-1 cells transfected with naked mouse membrane-form klotho plasmid DNA (pCAGGS-klotho) translated proper Klotho protein. This translated Klotho protein was secreted into the culture medium. Furthermore, ACE activity in human umbilical vein endothelial cells (HUVEC) was upregulated when HUVEC were co-cultured with COS-1 cells that were pre-transfected with pCAGGS-klotho. The conditioned medium from COS-1 cells pre-transfected with pCAGGS-klotho also dose-dependently upregulated ACE in HUVEC. In addition, the conditioned medium induced time- and dose-dependent enhancement of cAMP production in HUVEC. Rp-cAMP, an inhibitor of cAMP-dependent protein kinase A (PKA), inhibited the upregulation of ACE by Klotho protein. Our results suggest that mouse membrane-form Klotho protein acts as a humoral factor to increase ACE activity in HUVEC via a cAMP-PKA-dependent pathway. These findings may provide a new insight into the mechanism of Klotho protein.

• 出版日期2003-2-7