Zinc inhibits calcineurin activity in vitro by competing with nickel.
Calcineurin (CN) is a Ca(2+)/calmodulin (CaM)-dependent protein serine/threonine phosphatase that contains Zn(2+) in its catalytic domain and can be stimulated by divalent ions such as Mn(2+) and Ni(2+). In this study, the role of exogenous Zn(2+) in the regulation of CN activity and its relevance to the role of Ni(2+) was investigated. Zn(2+) at a concentration range of 10nM-10 micro M inhibited Ni(2+)-stimulated CN-activity in vitro in a dose-dependent manner and approximately 50% inhibition was attained with 0.25 micro M Zn(2+). Kinetic analysis showed that Zn(2+) inhibited the activity of CN by competing with Ni(2+). Interaction of CN and CaM was not inhibited with Zn(2+) at 10 micro M. Zn(2+) never affected the activity of cAMP phosphodiesterase 1 or myosin light-chain kinase (CaM-dependent enzymes) and rather activated alkaline phosphatase. The present results indicate that Zn(2+) should be a potent inhibitor for CN activity although this ion is essential for CN.
Takahashi
Katsunori
K
Department of Basic Sciences for Medicine, Gunma University School of Health Sciences, Japan.
Akaishi
Emi
E
Abe
Yumiko
Y
Ishikawa
Ryoki
R
Tanaka
Susumu
S
Hosaka
Kohei
K
Kubohara
Yuzuru
Y
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002147:Calmodulin / Q000378:metabolism; D020134:Catalytic Domain; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009532:Nickel / Q000378:metabolism*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D002147:Calmodulin; D009532:Nickel; D009219:Myosin-Light-Chain Kinase; D000469:Alkaline Phosphatase; D019703:Calcineurin; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; D015032:Zinc