Re: Phase 2 enzyme inducers appear to stop harmful inflammation

[Guest guest]

Hi All,

The article was:

Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14010-5. Epub 2005 Sep 19.

Divergent responses of chondrocytes and endothelial cells to shear stress:

Cross-talk among COX-2, the phase 2 response, and apoptosis.

Healy ZR, Lee NH, Gao X, Goldring MB, Talalay P, Kensler TW, Konstantopoulos K.

Fluid shear exerts anti-inflammatory and anti-apoptotic effects on

endothelial

cells by inducing the coordinated expression of phase 2 detoxifying and

antioxidant

genes. In contrast, high shear is pro-apoptotic in chondrocytes and promotes

matrix

degradation and cartilage destruction. We have analyzed the mechanisms

regulating

shear-mediated chondrocyte apoptosis by cDNA microarray technology and

bioinformatics. We demonstrate that shear-induced cyclooxygenase (COX)-2

suppresses

phosphatidylinositol 3-kinase (PI3-K) activity, which represses antioxidant

response

element (ARE)/NF-E2 related factor 2 (Nrf2)-mediated transcriptional response in

human chondrocytes. The resultant decrease in antioxidant capacity of sheared

chondrocytes contributes to their apoptosis. Phase 2 inducers, and to a lesser

extent COX-2-selective inhibitors, negate the shear-mediated suppression of

ARE-driven phase 2 activity and apoptosis. The abrogation of shear-induced COX-2

expression by PI3-K activity and/or stimulation of the Nrf2/ARE pathway suggests

the

existence of PI3-K/Nrf2/ARE negative feedback loops that potentially interfere

with

c-Jun N-terminal kinase 2 activity upstream of COX-2. Reconstructing the

signaling

network regulating shear-induced chondrocyte apoptosis may provide insights to

optimize conditions for culturing artificial cartilage in bioreactors and for

developing therapeutic strategies for arthritic disorders.

PMID: 16172382

A better paper may be the theoretically also pdf-available, that suggest that

oranges may be better is:

Am J Epidemiol. 2003 Feb 15;157(4):345-54.

Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older

women.

Cerhan JR, Saag KG, Merlino LA, Mikuls TR, Criswell LA.

The association of antioxidant vitamins and trace elements from foods and

supplements with risk of rheumatoid arthritis was evaluated in a prospective

cohort

study of 29,368 women who were aged 55-69 years at baseline in 1986. Through

1997,

152 cases of rheumatoid arthritis were identified. After controlling for other

risk

factors, greater intakes (highest tertile vs. lowest) of supplemental vitamin C

(relative risk (RR) = 0.70, 95% confidence interval (CI): 0.48, 1.09; p-trend =

0.08) and supplemental vitamin E (RR = 0.72, 95% CI: 0.47, 1.12; p-trend = 0.06)

were inversely associated with rheumatoid arthritis. There was no association

with

total carotenoids, alpha- or beta-carotene, lycopene, or lutein/zeaxanthin,

while

there was an inverse association with beta-cryptoxanthin (RR = 0.59, 95% CI:

0.39,

0.90; p-trend = 0.01). Greater use of supplemental zinc (RR = 0.39, 95% CI:

0.17,

0.88; p-trend = 0.03) was inversely associated with rheumatoid arthritis, while

any

use of supplemental copper (RR = 0.54, 95% CI: 0.28, 1.03) and manganese (RR =

0.50,

95% CI: 0.23, 1.07) showed suggestive inverse associations with rheumatoid

arthritis. Greater intakes of fruit (RR = 0.72, 95% CI: 0.46, 1.12; p-trend =

0.13)

and cruciferous vegetables (RR = 0.65, 95% CI: 0.42, 1.01; p-trend = 0.07) also

exhibited trends toward inverse associations with risk. When the antioxidants

were

modeled together, only beta-cryptoxanthin and supplemental zinc were

statistically

significant predictors. Intake of certain antioxidant micronutrients,

particularly

beta-cryptoxanthin and supplemental zinc, and possibly diets high in fruits and

cruciferous vegetables, may be protective against the development of rheumatoid

arthritis.

PMID: 12578805

--- drsusanforshey <drsusanforshey@...> wrote:

> Phytochemicals may protect cartilage, prevent pain in joints

He has

isolated compounds in edible plants that boost production of phase 2

enzymes. These phytochemicals can be found in cruciferous plants,

including broccoli.

Talalay provided one of the phase 2 inducers used in Healy's

experiments. " This was the first work done in applying these

phytochemicals to chondrocytes, which are constantly under the

influence of forces because of the way we move our joints, " Talalay

said. " The phase 2 inducers seemed to counteract the effects of that

stress by inhibiting the _expression of COX-2 enzyme. It's interesting

to think that people may be able to obtain this benefit through

dietary components. "

Al Pater, PhD; email: old542000@...

__________________________________

- PC Magazine Editors' Choice 2005

http://mail.

[Guest guest]

Hi All,

The article was:

Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14010-5. Epub 2005 Sep 19.

Divergent responses of chondrocytes and endothelial cells to shear stress:

Cross-talk among COX-2, the phase 2 response, and apoptosis.

Healy ZR, Lee NH, Gao X, Goldring MB, Talalay P, Kensler TW, Konstantopoulos K.

Fluid shear exerts anti-inflammatory and anti-apoptotic effects on

endothelial

cells by inducing the coordinated expression of phase 2 detoxifying and

antioxidant

genes. In contrast, high shear is pro-apoptotic in chondrocytes and promotes

matrix

degradation and cartilage destruction. We have analyzed the mechanisms

regulating

shear-mediated chondrocyte apoptosis by cDNA microarray technology and

bioinformatics. We demonstrate that shear-induced cyclooxygenase (COX)-2

suppresses

phosphatidylinositol 3-kinase (PI3-K) activity, which represses antioxidant

response

element (ARE)/NF-E2 related factor 2 (Nrf2)-mediated transcriptional response in

human chondrocytes. The resultant decrease in antioxidant capacity of sheared

chondrocytes contributes to their apoptosis. Phase 2 inducers, and to a lesser

extent COX-2-selective inhibitors, negate the shear-mediated suppression of

ARE-driven phase 2 activity and apoptosis. The abrogation of shear-induced COX-2

expression by PI3-K activity and/or stimulation of the Nrf2/ARE pathway suggests

the

existence of PI3-K/Nrf2/ARE negative feedback loops that potentially interfere

with

c-Jun N-terminal kinase 2 activity upstream of COX-2. Reconstructing the

signaling

network regulating shear-induced chondrocyte apoptosis may provide insights to

optimize conditions for culturing artificial cartilage in bioreactors and for

developing therapeutic strategies for arthritic disorders.

PMID: 16172382

A better paper may be the theoretically also pdf-available, that suggest that

oranges may be better is:

Am J Epidemiol. 2003 Feb 15;157(4):345-54.

Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older

women.

Cerhan JR, Saag KG, Merlino LA, Mikuls TR, Criswell LA.

The association of antioxidant vitamins and trace elements from foods and

supplements with risk of rheumatoid arthritis was evaluated in a prospective

cohort

study of 29,368 women who were aged 55-69 years at baseline in 1986. Through

1997,

152 cases of rheumatoid arthritis were identified. After controlling for other

risk

factors, greater intakes (highest tertile vs. lowest) of supplemental vitamin C

(relative risk (RR) = 0.70, 95% confidence interval (CI): 0.48, 1.09; p-trend =

0.08) and supplemental vitamin E (RR = 0.72, 95% CI: 0.47, 1.12; p-trend = 0.06)

were inversely associated with rheumatoid arthritis. There was no association

with

total carotenoids, alpha- or beta-carotene, lycopene, or lutein/zeaxanthin,

while

there was an inverse association with beta-cryptoxanthin (RR = 0.59, 95% CI:

0.39,

0.90; p-trend = 0.01). Greater use of supplemental zinc (RR = 0.39, 95% CI:

0.17,

0.88; p-trend = 0.03) was inversely associated with rheumatoid arthritis, while

any

use of supplemental copper (RR = 0.54, 95% CI: 0.28, 1.03) and manganese (RR =

0.50,

95% CI: 0.23, 1.07) showed suggestive inverse associations with rheumatoid

arthritis. Greater intakes of fruit (RR = 0.72, 95% CI: 0.46, 1.12; p-trend =

0.13)

and cruciferous vegetables (RR = 0.65, 95% CI: 0.42, 1.01; p-trend = 0.07) also

exhibited trends toward inverse associations with risk. When the antioxidants

were

modeled together, only beta-cryptoxanthin and supplemental zinc were

statistically

significant predictors. Intake of certain antioxidant micronutrients,

particularly

beta-cryptoxanthin and supplemental zinc, and possibly diets high in fruits and

cruciferous vegetables, may be protective against the development of rheumatoid

arthritis.

PMID: 12578805

--- drsusanforshey <drsusanforshey@...> wrote:

> Phytochemicals may protect cartilage, prevent pain in joints

He has

isolated compounds in edible plants that boost production of phase 2

enzymes. These phytochemicals can be found in cruciferous plants,

including broccoli.

Talalay provided one of the phase 2 inducers used in Healy's

experiments. " This was the first work done in applying these

phytochemicals to chondrocytes, which are constantly under the

influence of forces because of the way we move our joints, " Talalay

said. " The phase 2 inducers seemed to counteract the effects of that

stress by inhibiting the _expression of COX-2 enzyme. It's interesting

to think that people may be able to obtain this benefit through

dietary components. "

Al Pater, PhD; email: old542000@...

__________________________________

- PC Magazine Editors' Choice 2005

http://mail.