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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 l.jpg

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


Preventative target to reduce atherogenic risk in the elderly l.jpg

Preventative target to reduceatherogenic risk in the elderly


Slide3 l.jpg

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+


Slide4 l.jpg

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


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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


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


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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


Summary l.jpg

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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