Re: Lab study on H2O2 in vitro

[Guest guest]

Dear Deanna,

This experiment is an attempt to show in the laboratory how kidney cells

might be damaged in the body by hydrogen peroxide that is produced in

the body and not reduced to water and oxygen by the enzyme catalase.

Note that when catalase was introduced, the reaction was blocked.

( " Catalase pretreatment prevented the ... stimulation of TGF-beta1 mRNA " ).

So they have discovered that a lack of catalase will result in possible

damage to the kidneys through this specific pathway. Their next step might

be to find some drug that blocks this pathway. Of course, you wouldn't

expect them to look for something that increases the level of catalase.....

like ozone therapy.

Best of Health!

Dr. Saul Pressman, DCh, LOH

Re: Tampons -Women Read This!!!

>

> Saul....could you explain this study in layman terms for me? TY, Deanna

>

> Hydrogen peroxide increases extracellular matrix mRNA through TGF-beta in

human mesangial cells.

>

> Iglesias-De La Cruz MC, Ruiz- P, Alcami J, Diez-Marques L,

Ortega-Velazquez R, Chen S, -Puyol M, Ziyadeh FN, -Puyol D

>

> Departments of Physiology and Medicine, Alcala University, Madrid, Spain.

>

> [Record supplied by publisher]

>

> BACKGROUND: Reactive oxygen species (ROS) are excessively produced in

pathologic states, including many renal diseases. Transforming growth

factor-beta (TGF-beta) may mediate renal fibrotic injury, and ROS may act

through the TGF-beta pathway to exert a profibrotic effect. METHODS: The

expression of TGF-beta1 and extracellular matrix (ECM) components were

assessed in cultured human mesangial cells (HMCs) incubated with glucose

oxidase (GO), an enzyme that continuously generates hydrogen peroxide from

glucose. A neutralizing anti-TGF-beta antibody was added to test the

hypothesis that hydrogen peroxide acts through activation of the TGF-beta

pathway to stimulate ECM expression.

RESULTS: Northern blot analysis revealed significantly increased

steady-state levels of TGF-beta1 and ECM proteins (collagen types I, III,

and IV, and fibronectin) by approximately twofold. While no significant

effect on mRNA stability after treatment with GO was observed, other studies

employing promoter-reporter assays, competitive-quantitative reverse

transcription-polymerase chain reaction, mink lung epithelial cell

proliferation assay, and TGF-beta1 enzyme-linked immunosorbent assay all

demonstrated significant stimulation by GO (>1.5-fold) of TGF-beta1 promoter

activity, mRNA level, bioactivity, and protein production, respectively.

Catalase pretreatment prevented the GO-induced stimulation of TGF-beta1

mRNA. When incubations were performed with a panselective neutralizing

anti-TGF-beta antibody, the GO-stimulated expression of ECM molecules was

prevented.

CONCLUSIONS: GO-induced hydrogen peroxide production induces TGF-beta1

synthesis and thereby increases ECM gene expression in cultured HMCs. These

cellular responses may underlie the development and progression of renal

diseases characterized by oxidative stress.

>

> PMID: 11135061

[Guest guest]

Thank you Saul. Q: How does ozone therapy increase the level of catalase? I

understand HP uses catalase to produce oxygen...

Regards, Deanna

Saul Pressman <saul@...> wrote:

Dear Deanna,

This experiment is an attempt to show in the laboratory how kidney cells

might be damaged in the body by hydrogen peroxide that is produced in

the body and not reduced to water and oxygen by the enzyme catalase.

Note that when catalase was introduced, the reaction was blocked.

( " Catalase pretreatment prevented the ... stimulation of TGF-beta1 mRNA " ).

So they have discovered that a lack of catalase will result in possible

damage to the kidneys through this specific pathway. Their next step might

be to find some drug that blocks this pathway. Of course, you wouldn't

expect them to look for something that increases the level of catalase.....

like ozone therapy.

Best of Health!

Dr. Saul Pressman, DCh, LOH

Re: Tampons -Women Read This!!!

>

> Saul....could you explain this study in layman terms for me? TY, Deanna

>

> Hydrogen peroxide increases extracellular matrix mRNA through TGF-beta in

human mesangial cells.

>

> Iglesias-De La Cruz MC, Ruiz- P, Alcami J, Diez-Marques L,

Ortega-Velazquez R, Chen S, -Puyol M, Ziyadeh FN, -Puyol D

>

> Departments of Physiology and Medicine, Alcala University, Madrid, Spain.

>

> [Record supplied by publisher]

>

> BACKGROUND: Reactive oxygen species (ROS) are excessively produced in

pathologic states, including many renal diseases. Transforming growth

factor-beta (TGF-beta) may mediate renal fibrotic injury, and ROS may act

through the TGF-beta pathway to exert a profibrotic effect. METHODS: The

expression of TGF-beta1 and extracellular matrix (ECM) components were

assessed in cultured human mesangial cells (HMCs) incubated with glucose

oxidase (GO), an enzyme that continuously generates hydrogen peroxide from

glucose. A neutralizing anti-TGF-beta antibody was added to test the

hypothesis that hydrogen peroxide acts through activation of the TGF-beta

pathway to stimulate ECM expression.

RESULTS: Northern blot analysis revealed significantly increased

steady-state levels of TGF-beta1 and ECM proteins (collagen types I, III,

and IV, and fibronectin) by approximately twofold. While no significant

effect on mRNA stability after treatment with GO was observed, other studies

employing promoter-reporter assays, competitive-quantitative reverse

transcription-polymerase chain reaction, mink lung epithelial cell

proliferation assay, and TGF-beta1 enzyme-linked immunosorbent assay all

demonstrated significant stimulation by GO (>1.5-fold) of TGF-beta1 promoter

activity, mRNA level, bioactivity, and protein production, respectively.

Catalase pretreatment prevented the GO-induced stimulation of TGF-beta1

mRNA. When incubations were performed with a panselective neutralizing

anti-TGF-beta antibody, the GO-stimulated expression of ECM molecules was

prevented.

CONCLUSIONS: GO-induced hydrogen peroxide production induces TGF-beta1

synthesis and thereby increases ECM gene expression in cultured HMCs. These

cellular responses may underlie the development and progression of renal

diseases characterized by oxidative stress.

>

> PMID: 11135061

[Guest guest]

Dear Deanna,

I wouldn't say that hydrogen peroxide 'uses' catalase to produce oxygen.

Catalase is an enzyme normally produced in the body to reduce H2O2

to water and oxygen.

Ozone therapy has been shown in many experiments to cause the body to

sharply increase the amount of protective enzymes, specifically glutathione

peroxidase, superoxide dismutase, catalase and reductase. This results in

greater

protection for the cell from oxidation.

This is the underlying meaning for the phrase " beneficial oxidative stress " .

Best of Health!

Dr. Saul Pressman, DCh, LOH

Re: Tampons -Women Read This!!!

>

>

> >

> > Saul....could you explain this study in layman terms for me? TY, Deanna

> >

> > Hydrogen peroxide increases extracellular matrix mRNA through TGF-beta

in

> human mesangial cells.

> >

> > Iglesias-De La Cruz MC, Ruiz- P, Alcami J, Diez-Marques L,

> Ortega-Velazquez R, Chen S, -Puyol M, Ziyadeh FN, -Puyol

D

> >

> > Departments of Physiology and Medicine, Alcala University, Madrid,

Spain.

> >

> > [Record supplied by publisher]

> >

> > BACKGROUND: Reactive oxygen species (ROS) are excessively produced in

> pathologic states, including many renal diseases. Transforming growth

> factor-beta (TGF-beta) may mediate renal fibrotic injury, and ROS may act

> through the TGF-beta pathway to exert a profibrotic effect. METHODS: The

> expression of TGF-beta1 and extracellular matrix (ECM) components were

> assessed in cultured human mesangial cells (HMCs) incubated with glucose

> oxidase (GO), an enzyme that continuously generates hydrogen peroxide from

> glucose. A neutralizing anti-TGF-beta antibody was added to test the

> hypothesis that hydrogen peroxide acts through activation of the TGF-beta

> pathway to stimulate ECM expression.

>

> RESULTS: Northern blot analysis revealed significantly increased

> steady-state levels of TGF-beta1 and ECM proteins (collagen types I, III,

> and IV, and fibronectin) by approximately twofold. While no significant

> effect on mRNA stability after treatment with GO was observed, other

studies

> employing promoter-reporter assays, competitive-quantitative reverse

> transcription-polymerase chain reaction, mink lung epithelial cell

> proliferation assay, and TGF-beta1 enzyme-linked immunosorbent assay all

> demonstrated significant stimulation by GO (>1.5-fold) of TGF-beta1

promoter

> activity, mRNA level, bioactivity, and protein production, respectively.

> Catalase pretreatment prevented the GO-induced stimulation of TGF-beta1

> mRNA. When incubations were performed with a panselective neutralizing

> anti-TGF-beta antibody, the GO-stimulated expression of ECM molecules was

> prevented.

>

> CONCLUSIONS: GO-induced hydrogen peroxide production induces TGF-beta1

> synthesis and thereby increases ECM gene expression in cultured HMCs.

These

> cellular responses may underlie the development and progression of renal

> diseases characterized by oxidative stress.

> >

> > PMID: 11135061

>

>

>

>

>

>

>

>

[Guest guest]

Would hydorgen peroxide do this also??...Ron Inda

--- Saul Pressman <saul@...> wrote:

> Dear Deanna,

>

> I wouldn't say that hydrogen peroxide 'uses'

> catalase to produce oxygen.

> Catalase is an enzyme normally produced in the body

> to reduce H2O2

> to water and oxygen.

>

> Ozone therapy has been shown in many experiments to

> cause the body to

> sharply increase the amount of protective enzymes,

> specifically glutathione

> peroxidase, superoxide dismutase, catalase and

> reductase. This results in

> greater

> protection for the cell from oxidation.

>

> This is the underlying meaning for the phrase

> " beneficial oxidative stress " .

>

> Best of Health!

> Dr. Saul Pressman, DCh, LOH

> Re: Tampons -Women Read This!!!

> >

> >

> > >

> > > Saul....could you explain this study in layman

> terms for me? TY, Deanna

> > >

> > > Hydrogen peroxide increases extracellular matrix

> mRNA through TGF-beta

> in

> > human mesangial cells.

> > >

> > > Iglesias-De La Cruz MC, Ruiz- P, Alcami J,

> Diez-Marques L,

> > Ortega-Velazquez R, Chen S, -Puyol M,

> Ziyadeh FN, -Puyol

> D

> > >

> > > Departments of Physiology and Medicine, Alcala

> University, Madrid,

> Spain.

> > >

> > > [Record supplied by publisher]

> > >

> > > BACKGROUND: Reactive oxygen species (ROS) are

> excessively produced in

> > pathologic states, including many renal diseases.

> Transforming growth

> > factor-beta (TGF-beta) may mediate renal fibrotic

> injury, and ROS may act

> > through the TGF-beta pathway to exert a

> profibrotic effect. METHODS: The

> > expression of TGF-beta1 and extracellular matrix

> (ECM) components were

> > assessed in cultured human mesangial cells (HMCs)

> incubated with glucose

> > oxidase (GO), an enzyme that continuously

> generates hydrogen peroxide from

> > glucose. A neutralizing anti-TGF-beta antibody was

> added to test the

> > hypothesis that hydrogen peroxide acts through

> activation of the TGF-beta

> > pathway to stimulate ECM expression.

> >

> > RESULTS: Northern blot analysis revealed

> significantly increased

> > steady-state levels of TGF-beta1 and ECM proteins

> (collagen types I, III,

> > and IV, and fibronectin) by approximately twofold.

> While no significant

> > effect on mRNA stability after treatment with GO

> was observed, other

> studies

> > employing promoter-reporter assays,

> competitive-quantitative reverse

> > transcription-polymerase chain reaction, mink lung

> epithelial cell

> > proliferation assay, and TGF-beta1 enzyme-linked

> immunosorbent assay all

> > demonstrated significant stimulation by GO

> (>1.5-fold) of TGF-beta1

> promoter

> > activity, mRNA level, bioactivity, and protein

> production, respectively.

> > Catalase pretreatment prevented the GO-induced

> stimulation of TGF-beta1

> > mRNA. When incubations were performed with a

> panselective neutralizing

> > anti-TGF-beta antibody, the GO-stimulated

> expression of ECM molecules was

> > prevented.

> >

> > CONCLUSIONS: GO-induced hydrogen peroxide

> production induces TGF-beta1

> > synthesis and thereby increases ECM gene

> expression in cultured HMCs.

> These

> > cellular responses may underlie the development

> and progression of renal

> > diseases characterized by oxidative stress.

> > >

> > > PMID: 11135061

> >

> >

> >

> >

> >

> >

> >

> >

[Guest guest]

Dear Ron,

Good question. I don't know the answer. I have not read

many scientific papers about hydrogen peroxide. I do

know that when it is injected IV, it is readily broken down

in the blood because there is a great deal of catalase in the blood.

There is an organization that deals mostly with H2O2. It is called

IOMA, International Oxidative Medicine Association.

http://www.chfarr.com/oxidative_medicine.htm

They will be able to answer your question.

Best of Health!

Dr. Saul Pressman, DCh, LOH

Re: Tampons -Women Read This!!!

> > >

> > >

> > > >

> > > > Saul....could you explain this study in layman

> > terms for me? TY, Deanna

> > > >

> > > > Hydrogen peroxide increases extracellular matrix

> > mRNA through TGF-beta

> > in

> > > human mesangial cells.

> > > >

> > > > Iglesias-De La Cruz MC, Ruiz- P, Alcami J,

> > Diez-Marques L,

> > > Ortega-Velazquez R, Chen S, -Puyol M,

> > Ziyadeh FN, -Puyol

> > D

> > > >

> > > > Departments of Physiology and Medicine, Alcala

> > University, Madrid,

> > Spain.

> > > >

> > > > [Record supplied by publisher]

> > > >

> > > > BACKGROUND: Reactive oxygen species (ROS) are

> > excessively produced in

> > > pathologic states, including many renal diseases.

> > Transforming growth

> > > factor-beta (TGF-beta) may mediate renal fibrotic

> > injury, and ROS may act

> > > through the TGF-beta pathway to exert a

> > profibrotic effect. METHODS: The

> > > expression of TGF-beta1 and extracellular matrix

> > (ECM) components were

> > > assessed in cultured human mesangial cells (HMCs)

> > incubated with glucose

> > > oxidase (GO), an enzyme that continuously

> > generates hydrogen peroxide from

> > > glucose. A neutralizing anti-TGF-beta antibody was

> > added to test the

> > > hypothesis that hydrogen peroxide acts through

> > activation of the TGF-beta

> > > pathway to stimulate ECM expression.

> > >

> > > RESULTS: Northern blot analysis revealed

> > significantly increased

> > > steady-state levels of TGF-beta1 and ECM proteins

> > (collagen types I, III,

> > > and IV, and fibronectin) by approximately twofold.

> > While no significant

> > > effect on mRNA stability after treatment with GO

> > was observed, other

> > studies

> > > employing promoter-reporter assays,

> > competitive-quantitative reverse

> > > transcription-polymerase chain reaction, mink lung

> > epithelial cell

> > > proliferation assay, and TGF-beta1 enzyme-linked

> > immunosorbent assay all

> > > demonstrated significant stimulation by GO

> > (>1.5-fold) of TGF-beta1

> > promoter

> > > activity, mRNA level, bioactivity, and protein

> > production, respectively.

> > > Catalase pretreatment prevented the GO-induced

> > stimulation of TGF-beta1

> > > mRNA. When incubations were performed with a

> > panselective neutralizing

> > > anti-TGF-beta antibody, the GO-stimulated

> > expression of ECM molecules was

> > > prevented.

> > >

> > > CONCLUSIONS: GO-induced hydrogen peroxide

> > production induces TGF-beta1

> > > synthesis and thereby increases ECM gene

> > expression in cultured HMCs.

> > These

> > > cellular responses may underlie the development

> > and progression of renal

> > > diseases characterized by oxidative stress.

> > > >

> > > > PMID: 11135061

> > >

> > >

> > >

> > >

> > >

> > >

> > >

> > >

[Guest guest]

Saul,

Do you know how digestive enzymes (such as amylase) get into the blood?

They seem to serve useful purposes there. With leaky gut would more

digestive enzymes get into the gut, or maybe the gut leaks because there

haven't been enough?

J.

[Guest guest]

Thank you again Saul...Ron Inda

--- Saul Pressman <saul@...> wrote:

> Dear Ron,

>

> Good question. I don't know the answer. I have not

> read

> many scientific papers about hydrogen peroxide. I do

> know that when it is injected IV, it is readily

> broken down

> in the blood because there is a great deal of

> catalase in the blood.

>

> There is an organization that deals mostly with

> H2O2. It is called

> IOMA, International Oxidative Medicine Association.

> http://www.chfarr.com/oxidative_medicine.htm

> They will be able to answer your question.

>

> Best of Health!

> Dr. Saul Pressman, DCh, LOH

> Re: Tampons -Women Read

> This!!!

> > > >

> > > >

> > > > >

> > > > > Saul....could you explain this study in

> layman

> > > terms for me? TY, Deanna

> > > > >

> > > > > Hydrogen peroxide increases extracellular

> matrix

> > > mRNA through TGF-beta

> > > in

> > > > human mesangial cells.

> > > > >

> > > > > Iglesias-De La Cruz MC, Ruiz- P,

> Alcami J,

> > > Diez-Marques L,

> > > > Ortega-Velazquez R, Chen S, -Puyol M,

> > > Ziyadeh FN, -Puyol

> > > D

> > > > >

> > > > > Departments of Physiology and Medicine,

> Alcala

> > > University, Madrid,

> > > Spain.

> > > > >

> > > > > [Record supplied by publisher]

> > > > >

> > > > > BACKGROUND: Reactive oxygen species (ROS)

> are

> > > excessively produced in

> > > > pathologic states, including many renal

> diseases.

> > > Transforming growth

> > > > factor-beta (TGF-beta) may mediate renal

> fibrotic

> > > injury, and ROS may act

> > > > through the TGF-beta pathway to exert a

> > > profibrotic effect. METHODS: The

> > > > expression of TGF-beta1 and extracellular

> matrix

> > > (ECM) components were

> > > > assessed in cultured human mesangial cells

> (HMCs)

> > > incubated with glucose

> > > > oxidase (GO), an enzyme that continuously

> > > generates hydrogen peroxide from

> > > > glucose. A neutralizing anti-TGF-beta antibody

> was

> > > added to test the

> > > > hypothesis that hydrogen peroxide acts through

> > > activation of the TGF-beta

> > > > pathway to stimulate ECM expression.

> > > >

> > > > RESULTS: Northern blot analysis revealed

> > > significantly increased

> > > > steady-state levels of TGF-beta1 and ECM

> proteins

> > > (collagen types I, III,

> > > > and IV, and fibronectin) by approximately

> twofold.

> > > While no significant

> > > > effect on mRNA stability after treatment with

> GO

> > > was observed, other

> > > studies

> > > > employing promoter-reporter assays,

> > > competitive-quantitative reverse

> > > > transcription-polymerase chain reaction, mink

> lung

> > > epithelial cell

> > > > proliferation assay, and TGF-beta1

> enzyme-linked

> > > immunosorbent assay all

> > > > demonstrated significant stimulation by GO

> > > (>1.5-fold) of TGF-beta1

> > > promoter

> > > > activity, mRNA level, bioactivity, and protein

> > > production, respectively.

> > > > Catalase pretreatment prevented the GO-induced

> > > stimulation of TGF-beta1

> > > > mRNA. When incubations were performed with a

> > > panselective neutralizing

> > > > anti-TGF-beta antibody, the GO-stimulated

> > > expression of ECM molecules was

> > > > prevented.

> > > >

> > > > CONCLUSIONS: GO-induced hydrogen peroxide

> > > production induces TGF-beta1

> > > > synthesis and thereby increases ECM gene

> > > expression in cultured HMCs.

>

=== message truncated ===

__________________________________________________

[Guest guest]

Thank you Saul. That site mentions HP by intravenous. I'm looking into the

safest way to get oxygen orally....the information out there is so confusing.

Deanna

Saul Pressman <saul@...> wrote:

Dear Ron,

Good question. I don't know the answer. I have not read

many scientific papers about hydrogen peroxide. I do

know that when it is injected IV, it is readily broken down

in the blood because there is a great deal of catalase in the blood.

There is an organization that deals mostly with H2O2. It is called

IOMA, International Oxidative Medicine Association.

http://www.chfarr.com/oxidative_medicine.htm

They will be able to answer your question.

Best of Health!

Dr. Saul Pressman, DCh, LOH

Re: Tampons -Women Read This!!!

> > >

> > >

> > > >

> > > > Saul....could you explain this study in layman

> > terms for me? TY, Deanna

> > > >

> > > > Hydrogen peroxide increases extracellular matrix

> > mRNA through TGF-beta

> > in

> > > human mesangial cells.

> > > >

> > > > Iglesias-De La Cruz MC, Ruiz- P, Alcami J,

> > Diez-Marques L,

> > > Ortega-Velazquez R, Chen S, -Puyol M,

> > Ziyadeh FN, -Puyol

> > D

> > > >

> > > > Departments of Physiology and Medicine, Alcala

> > University, Madrid,

> > Spain.

> > > >

> > > > [Record supplied by publisher]

> > > >

> > > > BACKGROUND: Reactive oxygen species (ROS) are

> > excessively produced in

> > > pathologic states, including many renal diseases.

> > Transforming growth

> > > factor-beta (TGF-beta) may mediate renal fibrotic

> > injury, and ROS may act

> > > through the TGF-beta pathway to exert a

> > profibrotic effect. METHODS: The

> > > expression of TGF-beta1 and extracellular matrix

> > (ECM) components were

> > > assessed in cultured human mesangial cells (HMCs)

> > incubated with glucose

> > > oxidase (GO), an enzyme that continuously

> > generates hydrogen peroxide from

> > > glucose. A neutralizing anti-TGF-beta antibody was

> > added to test the

> > > hypothesis that hydrogen peroxide acts through

> > activation of the TGF-beta

> > > pathway to stimulate ECM expression.

> > >

> > > RESULTS: Northern blot analysis revealed

> > significantly increased

> > > steady-state levels of TGF-beta1 and ECM proteins

> > (collagen types I, III,

> > > and IV, and fibronectin) by approximately twofold.

> > While no significant

> > > effect on mRNA stability after treatment with GO

> > was observed, other

> > studies

> > > employing promoter-reporter assays,

> > competitive-quantitative reverse

> > > transcription-polymerase chain reaction, mink lung

> > epithelial cell

> > > proliferation assay, and TGF-beta1 enzyme-linked

> > immunosorbent assay all

> > > demonstrated significant stimulation by GO

> > (>1.5-fold) of TGF-beta1

> > promoter

> > > activity, mRNA level, bioactivity, and protein

> > production, respectively.

> > > Catalase pretreatment prevented the GO-induced

> > stimulation of TGF-beta1

> > > mRNA. When incubations were performed with a

> > panselective neutralizing

> > > anti-TGF-beta antibody, the GO-stimulated

> > expression of ECM molecules was

> > > prevented.

> > >

> > > CONCLUSIONS: GO-induced hydrogen peroxide

> > production induces TGF-beta1

> > > synthesis and thereby increases ECM gene

> > expression in cultured HMCs.

> > These

> > > cellular responses may underlie the development

> > and progression of renal

> > > diseases characterized by oxidative stress.

> > > >

> > > > PMID: 11135061

> > >

> > >

> > >

> > >

> > >

> > >

> > >

> > >

[Guest guest]

Dear Deanna,

The safest way to get oxygen orally is ozonated water.

Unfortunately, its not the cheapest....

Best of Health!

Dr. Saul Pressman, DCh, LOH

Re: Tampons -Women Read This!!!

> > > >

> > > >

> > > > >

> > > > > Saul....could you explain this study in layman

> > > terms for me? TY, Deanna

> > > > >

> > > > > Hydrogen peroxide increases extracellular matrix

> > > mRNA through TGF-beta

> > > in

> > > > human mesangial cells.

> > > > >

> > > > > Iglesias-De La Cruz MC, Ruiz- P, Alcami J,

> > > Diez-Marques L,

> > > > Ortega-Velazquez R, Chen S, -Puyol M,

> > > Ziyadeh FN, -Puyol

> > > D

> > > > >

> > > > > Departments of Physiology and Medicine, Alcala

> > > University, Madrid,

> > > Spain.

> > > > >

> > > > > [Record supplied by publisher]

> > > > >

> > > > > BACKGROUND: Reactive oxygen species (ROS) are

> > > excessively produced in

> > > > pathologic states, including many renal diseases.

> > > Transforming growth

> > > > factor-beta (TGF-beta) may mediate renal fibrotic

> > > injury, and ROS may act

> > > > through the TGF-beta pathway to exert a

> > > profibrotic effect. METHODS: The

> > > > expression of TGF-beta1 and extracellular matrix

> > > (ECM) components were

> > > > assessed in cultured human mesangial cells (HMCs)

> > > incubated with glucose

> > > > oxidase (GO), an enzyme that continuously

> > > generates hydrogen peroxide from

> > > > glucose. A neutralizing anti-TGF-beta antibody was

> > > added to test the

> > > > hypothesis that hydrogen peroxide acts through

> > > activation of the TGF-beta

> > > > pathway to stimulate ECM expression.

> > > >

> > > > RESULTS: Northern blot analysis revealed

> > > significantly increased

> > > > steady-state levels of TGF-beta1 and ECM proteins

> > > (collagen types I, III,

> > > > and IV, and fibronectin) by approximately twofold.

> > > While no significant

> > > > effect on mRNA stability after treatment with GO

> > > was observed, other

> > > studies

> > > > employing promoter-reporter assays,

> > > competitive-quantitative reverse

> > > > transcription-polymerase chain reaction, mink lung

> > > epithelial cell

> > > > proliferation assay, and TGF-beta1 enzyme-linked

> > > immunosorbent assay all

> > > > demonstrated significant stimulation by GO

> > > (>1.5-fold) of TGF-beta1

> > > promoter

> > > > activity, mRNA level, bioactivity, and protein

> > > production, respectively.

> > > > Catalase pretreatment prevented the GO-induced

> > > stimulation of TGF-beta1

> > > > mRNA. When incubations were performed with a

> > > panselective neutralizing

> > > > anti-TGF-beta antibody, the GO-stimulated

> > > expression of ECM molecules was

> > > > prevented.

> > > >

> > > > CONCLUSIONS: GO-induced hydrogen peroxide

> > > production induces TGF-beta1

> > > > synthesis and thereby increases ECM gene

> > > expression in cultured HMCs.

> > > These

> > > > cellular responses may underlie the development

> > > and progression of renal

> > > > diseases characterized by oxidative stress.

> > > > >

> > > > > PMID: 11135061

> > > >

> > > >

> > > >

> > > >

> > > >

> > > >

> > > >

> > > >