TY - JOUR
T1 - Ni2+, a double-acting inhibitor of neuronal nitric oxide synthase interfering with L-arginine binding and Ca2+/calmodulin-dependent enzyme activation
AU - Palumbo, Anna
AU - Astarita, Giuseppe
AU - Picardo, Mauro
AU - D'Ischia, Marco
PY - 2001
Y1 - 2001
N2 - Ni2+, a toxic and carcinogenic pollutant and one of the leading causes of contact dermatitis, is shown to inhibit neuronal nitric oxide synthase (nNOS) in a competitive, reversible manner with respect to the substrate L-arginine (Ki = 30 ± 4 μM). The IC50 values were dependent on calmodulin (CAM) concentration, but proved independent of Ca2+, tetrahydrobiopterin (BH4) and other essential cofactors. Ni2+ also inhibited CAM-dependent cytochrome c reduction, NADPH oxidation, and H2O2 production by nNOS. Overall, the action profile of Ni2+ was suggestive of an unusual, double-acting inhibitor of nNOS affecting L-arginine-binding and Ca2+/CAM-dependent enzyme activation.
AB - Ni2+, a toxic and carcinogenic pollutant and one of the leading causes of contact dermatitis, is shown to inhibit neuronal nitric oxide synthase (nNOS) in a competitive, reversible manner with respect to the substrate L-arginine (Ki = 30 ± 4 μM). The IC50 values were dependent on calmodulin (CAM) concentration, but proved independent of Ca2+, tetrahydrobiopterin (BH4) and other essential cofactors. Ni2+ also inhibited CAM-dependent cytochrome c reduction, NADPH oxidation, and H2O2 production by nNOS. Overall, the action profile of Ni2+ was suggestive of an unusual, double-acting inhibitor of nNOS affecting L-arginine-binding and Ca2+/CAM-dependent enzyme activation.
KW - Calmodulin
KW - Neuronal nitric oxide synthase inhibition
KW - Nickel ions
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U2 - 10.1006/bbrc.2001.5129
DO - 10.1006/bbrc.2001.5129
M3 - Article
C2 - 11437384
AN - SCOPUS:0034798526
VL - 285
SP - 142
EP - 146
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -