NADH oxidase of liver plasma membrane stimulated by diferric transferrin and neoplastic transformation induced by the carcinogen 2-acetylaminofluorene

The activity of a hormone- and growth-factor-stimulated NADH oxidase of the rat liver plasma membrane responds to guanine nucleotides, but in a manner that differs from that of the classic trimeric and low-molecular-mass monomeric G-proteins. In the absence of added bivalent ions, both GTP and GDP as well as guanosine 5′-[gamma-thio]triphosphate (GTP[gamma-S]) but not guanosine 5′[beta-thio]diphosphate (GDP[beta-S]) stimulate the activity over the range 1 microM to 100 microM. Other di- and tri-nucleotides also stimulate, but only at concentrations of 100 microM or higher. Added bivalent ions are not required either for NADH oxidation or guanine nucleotide stimulation. Bivalent ions (Mg2+ > Mn2+ > or = Ca2+) alone stimulate only slightly at low concentrations and then inhibit at high concentrations. The inhibitions are augmented by GDP or GTP [gamma-S] but not by GTP. Although the activity is the same, or less, in the presence of 0.5 mM MgCl2, GTP at 1-100 nM and other nucleotides at 0.1 mM or 1 mM still stimulate in its presence. The NADH oxidase is activated by mastoparan but aluminum fluoride is weakly inhibitory. Cholera and pertussis toxins elicit only marginal responses. Both the Mg2+ and the GDP and GTP[gamma-S] inhibitions (but not the GTP stimulations) shift to higher concentrations when the membrane preparations are first solubilized with Triton X-100. The results suggest a role for guanine nucleotides in the regulation of plasma membrane NADH oxidase, but with properties that differ from those of either trimeric or the low-molecular-mass G proteins thus far described.

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NADH diferric transferrin reductase in liver plasma membrane.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)47676-4 ◽

1987 ◽

Vol 262 (33) ◽

pp. 15915-15921 ◽

Cited By ~ 8

Author(s):

I L Sun ◽

P Navas ◽

F L Crane ◽

D J Morré ◽

H Löw

Keyword(s):

Plasma Membrane ◽

Liver Plasma Membrane ◽

Diferric Transferrin

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A growth factor- and hormone-stimulated NADH oxidase from rat liver plasma membrane

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/0005-2736(92)90168-l ◽

1992 ◽

Vol 1105 (1) ◽

pp. 109-117 ◽

Cited By ~ 106

Author(s):

Andrew O. Brightman ◽

Juan Wang ◽

Raymond Kin-man Miu ◽

Iris L. Sun ◽

Rita Barr ◽

...

Keyword(s):

Plasma Membrane ◽

Growth Factor ◽

Rat Liver ◽

Nadh Oxidase ◽

Liver Plasma Membrane

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The Oxidative Function of Diferric Transferrin

Biochemistry Research International ◽

10.1155/2012/592806 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Frederick L. Crane ◽

Hans Löw

Keyword(s):

Plasma Membrane ◽

Iron Uptake ◽

Plasma Membranes ◽

Nadh Oxidase ◽

Growth Promotion ◽

Terminal Oxidase ◽

Diferric Transferrin ◽

Oxidative Function ◽

Stimulation Of

There is evidence for an unexpected role of diferric transferrin as a terminal oxidase for the transplasma membrane oxidation of cytosolic NADH. In the original studies which showed the reduction of iron in transferrin by the plasma membranes NADH oxidase, the possible role of the reduction on iron uptake was emphasized. The rapid reoxidation of transferrin iron under aerobic conditions precludes a role for surface reduction at neutral pH for release of iron for uptake at the plasma membrane. The stimulation of cytosolic NADH oxidation by diferric transferrin indicates that the transferrin can act as a terminal oxidase for the transplasma membrane NADH oxidase or can bind to a site which activates the oxidase. Since plasma membrane NADH oxidases clearly play a role in cell signaling, the relation of ferric transferrin stimulation of NADH oxidase to cell control should be considered, especially in relation to the growth promotion by transferrin not related to iron uptake. The oxidase can also contribute to control of cytosolic NAD concentration, and thereby can activate sirtuins for control of ageing and growth.

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