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 reduceatherogenic risk in the elderly

NOX

QuinoneReductase

Q10 Q10H2

1/2 O2 H2O

NAD(P)H + H+

NAD(P)+

ProteinS

SProteinOutside

Inside

Pla

sma

Mem

bra

ne

2 O2

2 O2-

SH

SH

Glucose

Pyruvate

ATP

NADH + H+

ADP

Gly

co

lys

is NAD++

MitochondrialDNA mutations

Anaerobic Cell

ATP Production by Glycolysis

Enhanced PMOR Activity to Oxidize NADH

Propagation of Response

LDL

oxLDL

Atherosclerosis

Glucose

Pyruvate

NADH + H+

+

Gly

co

lys

is NAD+

AH2

A

PMOR

2 H+

+2 e-

-

2

1/2 O2

H O

Generation of ROS at PM

.

O2-

H2O2

OH•

Adjacent cells

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

Ferricytochrome c reductionHuman 20 – 40y 50 – 70y

nmoles/min/106 cells

Buffy coats

+SOD

0.02

0.02

.06

.02

nmoles/min/mlSera

+SOD

0.1

0.1

0.3

0.1

Saliva

+SOD

0.15

0.1

0.5

0.1

nmoles/min/Osteopatch

Perspiration

+SOD

0.03

0.03

0.3

0.03

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

• Coenzyme Q (Q8, Q9 and Q10 but not by Q0, Q2, Q4, or Q7)

• Several Chinese botanicals with antiaging activitiesMorré, D.M and Morré, D.J. 2003 BioFactors 18:33-43

Buffy Coats

Ar NOX inhibited by

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