arnox aging related cell surface ecto nox protein
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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

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

slide3

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

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

sod inhibited reduction of ferricytochrome c
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
slide7

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
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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