Transgenic overexpression of translationally controlled tumor protein induces systemic hypertension via repression of Na+,K+-ATPase.
Inhibition of Na(+),K(+)-ATPase has been implicated in the pathogenesis of hypertension via its effect on smooth muscle reactivity and myocardial contractility. We recently demonstrated that translationally controlled tumor protein (TCTP) interacts with the 3rd cytoplasmic domain of Na(+),K(+)-ATPase alpha(1)-subunit and acts as its cytoplasmic repressor. Therefore, we hypothesized that repression of Na(+),K(+)-ATPase by overexpressed TCTP might underlie the development of hypertension. In the present study, we confirmed that transgenic mice overexpressing TCTP developed systemic arterial hypertension at about 6 weeks after birth. Vascular smooth muscle of TCTP-overexpressing transgenic mice also displayed augmented contractile response to vasoconstrictors and attenuated relaxation response to vasodilators. These responses seem to be caused by reduced Na(+),K(+)-ATPase activity and increased intracellular calcium, suggesting that inhibition of Na(+),K(+)-ATPase by overexpression of TCTP is involved in the pathogenesis of hypertension. This study provides a new link between alteration of sodium pump activity and hypertension in vivo, and suggests that TCTP might be a therapeutic target for the treatment of hypertension.
Kim
Min-Jeong
MJ
College of Pharmacy, Center for Cell Signalling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
Kwon
Jin-Sook
JS
Suh
Suk Hyo
SH
Suh
Jae-Kyung
JK
Jung
Jaehoon
J
Lee
Si-Nae
SN
Kim
Young-Hwa
YH
Cho
Myeong-Chan
MC
Oh
Goo Taeg
GT
Lee
Kyunglim
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D001794:Blood Pressure; D020013:Calcium Signaling; D002645:Chickens; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology*; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1; D014463:Ultrasonography
D014408:Biomarkers, Tumor; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D000254:Sodium-Potassium-Exchanging ATPase