Age-Related ENOX Proteins (arNOX)

  • D. James Morré
  • Dorothy M. Morré


Age-related ENOX proteins (arNOX/ENOX3) of the cell surface and endosomes with a period length of 26 min and shed into body fluids increase linearly with age beginning at about 30 years to a maximum at about age 60. Rather than only reducing oxygen to water as is characteristic of ENOX1 and ENOX2, arNOX proteins transfer electrons to oxygen to form superoxide during part of their functional cycle. By generating oxygen species at the cell surface and in body fluids (saliva, serum, perspiration, urine, interstitial fluids), arNOX proteins propagate reactive oxygen species to surrounding cells and circulating lipoprotein particles as occurs in skin aging and atherogenesis. arNOX is widely distributed among aged systems including late passage cultured cells and plants. Activity is inhibited by coenzyme Q, salicin used in skin care, and oral supplements to reduce lipoprotein oxidation leading to coronary heart disease. The arNOX protein family has been identified in yeast and humans and has been cloned. At least five arNOX protein family members (TM9SF1-5) have been identified in yeast and in humans. Synthesized as membrane anchored proteins with their catalytic N-termini directed toward the cells’ exterior, a ca. 30-kDa fragment is shed and enters the blood and other body fluids or is internalized into endosomes. A particular family member, TM9SF2 with sequence homology to the LDL receptor, binds to the AopB100 proteins of LDLs as a source of electrons for transfer to oxygen to form superoxide. The hydrogen peroxide resulting from dismutation of the superoxide results in oxidation of the lipid core of the LDL with formation of malondialdehyde-like adducts, a prerequisite for their internalization by macrophages to form foam cells, the obligate progenitors of atherosclerotic plaques. Other than superoxide production, molecular structure and response to inhibitors, arNOX proteins share many properties with other ENOX proteins including a cell surface location, the oscillatory pattern of activity, resistance to proteases, N-terminal sequencing and chemical degradation, and a propensity for the purified proteins to form aggregates. They carry out both NADH (hydroquinone) oxidation and protein disulfide-thiol interchange as determined from studies with recombinant arNOX protein family members.


Superoxide Production Period Length Protein Thiol Skin Aging Advanced Glycation Endproduct 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer Science+Business Media New York 2012

Authors and Affiliations

  • D. James Morré
    • 1
  • Dorothy M. Morré
    • 1
  1. 1.Mor-NuCo, LLCPurdue Research ParkWest LafayetteUSA

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