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arNOX, AGING-RELATED CELL SURFACE ECTO-NOX PROTEIN

arNOX, AGING-RELATED CELL SURFACE ECTO-NOX PROTEIN. D. James Morr é and Dorothy Morr é Department of Medicinal Chemistry & Molecular Pharmacology and Department of Foods and Nutrition Purdue University, W. Lafayette, Indiana 47907. Preventative target to reduce atherogenic risk in the elderly.

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arNOX, AGING-RELATED CELL SURFACE ECTO-NOX PROTEIN

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  1. arNOX, AGING-RELATED CELL SURFACE ECTO-NOX PROTEIN D. James Morré and Dorothy Morré Department of Medicinal Chemistry & Molecular Pharmacology and Department of Foods and Nutrition Purdue University, W. Lafayette, Indiana 47907

  2. Preventative target to reduceatherogenic risk in the elderly

  3. 1/2 O2 H2O - 2 O2 NOX 2 O2 S SH Protein Protein Outside S SH Plasma Membrane Q10 Q10H2 Inside Quinone Reductase NAD(P)+ NAD(P)H + H+

  4. Glucose Glucose ADP NAD + NAD+ + A Glycolysis Glycolysis ATP PMOR NADH NADH AH + H+ + + H+ 2 Pyruvate Pyruvate Anaerobic Mitochondrial ATP Production Enhanced PMOR Activity Cell DNA mutations by Glycolysis to Oxidize NADH Adjacent cells LDL - O 2 1/2 O 2 2 H+ + Atherosclerosis 2 e- - H O 2 . oxLDL H O 2 2 OH• Generation of Propagation ROS at PM of Response

  5. SOD – inhibited reduction of ferricytochrome c Human (Age > 50y) • Buffy coats • Sera • Saliva • Perspiration Late-passage cell culture • MCF-10A • WI-38 Plants • Senescent spinach leaves • Senescent Aracean spathes

  6. Morré, D.M, F. Guo and Morré, D.J. 2003 Mol. Cell. Biochem. 254:101-109.

  7. Ar NOX inhibited by • Coenzyme Q (Q8, Q9 and Q10 but not by Q0, Q2, Q4, or Q7) • Several Chinese botanicals with antiaging activities Buffy Coats Morré, D.M and Morré, D.J. 2003 BioFactors 18:33-43

  8. Summary Aging-related NOX • Generates superoxide • Cells and sera of aged individual (>50y) • Postulated to propagate aging cascade to adjacent cells and circulating lipoproteins • Ablated by coenzyme Q10 /Antiaging botanicals

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