Re: Glutathione depletion, RNase-L cleavage, and viral reactivation

[Guest guest]

Hi Rich,

I have to use a medical dictionary when I read your posts. Thanks. I'm not

being sarcastic. I think it's terrific that we have people on this list who

know so much that I can't understand their posts without a little study.

Today I had to look up " antiporter " in order to understand this sentence you

wrote:

> Well, today I found a paper from the U. of Rome group (first abstract below)

> that suggests that glutathione depletion leads to oxidative stress, which

> inhibits the action of the sodium/hydrogen antiporter, causing a drop in the

> pH in the cell, and this then leads to viral replication.

One definition led to another, and I ended up with a whole list:

Antiporters

Membrane transporters that co-transport two or more dissimilar molecules in

the opposite direction across a membrane. Usually the transport of one ion

or molecule is against its electrochemical gradient and is " powered " by the

movement of another ion or molecule with its electrochemical gradient.

Antiporter, Sodium-Hydrogen

A plasma membrane exchange glycoprotein transporter that functions in

intracellular pH regulation, cell volume regulation, and cellular response

to many different hormones and mitogens.

Caspases

A family of intracellular CYSTEINE ENDOPEPTIDASES. They play a key role in

inflammation and mammalian APOPTOSIS. They are specific for aspartic acid at

the P1 position. They are divided into two classes based on the lengths of

their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have long

prodomains and -3,-6,-7,-9 have short prodomains. EC 3.4.22.-.

Cysteine Endopeptidases

ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This

group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22.

Endopeptidases

A subclass of PEPTIDE HYDROLASES. They are classified primarily by their

catalytic mechanism. Specificity is used only for identification of

individual enzymes. They comprise the SERINE ENDOPEPTIDASES, EC 3.4.21;

CYSTEINE ENDOPEPTIDASES, EC 3.4.22; ASPARTIC ENDOPEPTIDASES, EC 3.4.23,

METALLOENDOPEPTIDASES, EC 3.4.24; and a group of enzymes yet to be assigned

to any of the above sub-classes, EC 3.4.99. EC 3.4.-.

Hydrolases

Any member of the class of enzymes that catalyze the cleavage of the

substrate and the addition of water to the resulting molecules, e.g.,

ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES,

peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER

HYDROLASES). EC 3.

Peptide Hydrolases

A subclass of enzymes from the hydrolase class that catalyze the hydrolysis

of peptide bonds. EXOPEPTIDASES and ENDOPEPTIDASES make up the

sub-subclasses for this group. EC 3.4.

http://www.online-medical-dictionary.org/

Sue B.,

Upstate New York

[Guest guest]

Hi, Sue.

Those definitions are great! I was particularly interested to read

that the cysteine endopeptidases compose a group of enzymes that are

inactivated by sulfhydryl reagents. Glutathione is a sulfhydryl

reagent, so this all fits together really well. If glutathione

becomes depleted, the cysteine endopeptidases may just have a field

day,chopping up enzymes, including RNase-L.

Thanks for doing all that work!

Rich

>

> > Well, today I found a paper from the U. of Rome group (first

abstract below)

> > that suggests that glutathione depletion leads to oxidative

stress, which

> > inhibits the action of the sodium/hydrogen antiporter, causing a

drop in the

> > pH in the cell, and this then leads to viral replication.

>

> One definition led to another, and I ended up with a whole list:

>

> Antiporters

> Membrane transporters that co-transport two or more dissimilar

molecules in

> the opposite direction across a membrane. Usually the transport of

one ion

> or molecule is against its electrochemical gradient and

is " powered " by the

> movement of another ion or molecule with its electrochemical

gradient.

>

> Antiporter, Sodium-Hydrogen

> A plasma membrane exchange glycoprotein transporter that functions

in

> intracellular pH regulation, cell volume regulation, and cellular

response

> to many different hormones and mitogens.

>

> Caspases

> A family of intracellular CYSTEINE ENDOPEPTIDASES. They play a key

role in

> inflammation and mammalian APOPTOSIS. They are specific for

aspartic acid at

> the P1 position. They are divided into two classes based on the

lengths of

> their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have

long

> prodomains and -3,-6,-7,-9 have short prodomains. EC 3.4.22.-.

>

> Cysteine Endopeptidases

> ENDOPEPTIDASES which have a cysteine involved in the catalytic

process. This

> group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22.

>

> Endopeptidases

> A subclass of PEPTIDE HYDROLASES. They are classified primarily by

their

> catalytic mechanism. Specificity is used only for identification of

> individual enzymes. They comprise the SERINE ENDOPEPTIDASES, EC

3.4.21;

> CYSTEINE ENDOPEPTIDASES, EC 3.4.22; ASPARTIC ENDOPEPTIDASES, EC

3.4.23,

> METALLOENDOPEPTIDASES, EC 3.4.24; and a group of enzymes yet to be

assigned

> to any of the above sub-classes, EC 3.4.99. EC 3.4.-.

>

> Hydrolases

> Any member of the class of enzymes that catalyze the cleavage of

the

> substrate and the addition of water to the resulting molecules,

e.g.,

> ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases,

NUCLEOTIDASES,

> peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC

MONOESTER

> HYDROLASES). EC 3.

>

> Peptide Hydrolases

> A subclass of enzymes from the hydrolase class that catalyze the

hydrolysis

> of peptide bonds. EXOPEPTIDASES and ENDOPEPTIDASES make up the

> sub-subclasses for this group. EC 3.4.

>

> http://www.online-medical-dictionary.org/

>

> Sue B.,

> Upstate New York

[Guest guest]

Hi Rich,

> Later on, PWCs may pick up other, exogenous ( " externally-born " ) viral and

> intracellular bacterial infections

Would you classify Borrelia burgdorferei as an intracellular infection?

> Well, today I found a paper from the U. of Rome group (first abstract below)

> that suggests that glutathione depletion leads to oxidative stress, which

> inhibits the action of the sodium/hydrogen antiporter, causing a drop in the

> pH in the cell, and this then leads to viral replication.

Since they found a drop in the pH of the canine kidney cells they studied,

[did I get that right?] do you think the same drop would occur in all of the

cells in the dog (or human)? Or in some types of cells more than others?

Sue B.,

Upstate New York

[Guest guest]

Hi, Sue.

> Hi Rich,

>

> > Later on, PWCs may pick up other, exogenous ( " externally-born " )

viral and

> > intracellular bacterial infections

>

> Would you classify Borrelia burgdorferei as an intracellular

infection?

No, Borrelia are spirochetes (helical corkscrew-like bacteria) about

20 to 30 microns in length. They have their own cells.

>

> > Well, today I found a paper from the U. of Rome group (first

abstract below)

> > that suggests that glutathione depletion leads to oxidative

stress, which

> > inhibits the action of the sodium/hydrogen antiporter, causing a

drop in the

> > pH in the cell, and this then leads to viral replication.

>

> Since they found a drop in the pH of the canine kidney cells they

studied,

> [did I get that right?] do you think the same drop would occur in

all of the

> cells in the dog (or human)? Or in some types of cells more than

others?

I think the same drop would occur in any cell that suffered

glutathione depletion, since all cells use sodium/hydrogen

antiporters to control their pH. However, in the human body,

glutathione is compartmentalized, which means that it can have

different concentrations in different organs or cell types. When

supplies of glutathione precursors (particularly cysteine) are in

short supply to the total organism (the human body as a whole), some

organs and cell types run low on glutathione before others do,

either because of poorer access to the limited amounts of precursors

or because they express the enzymes used to make glutathione in

lower concentrations, the degree of expression being characteristic

of the particular organ or cell type. Skeletal muscle cells seem to

be the first to feel the pinch.

>

> Sue B.,

> Upstate New York

Rich