Ironjustic
Wed, Jun-21-06, 06:16
<<snip>> HSP60, is able to shut down the autoimmune response
causing this disorder <<snip>> <<snip>> Hsp60 prevents the
release of iron ions <<snip>>
Public release date: 19-Jun-2006
Contact: Jennifer Manning jennifer@acwis.org 212-895-7952
American Committee for the Weizmann Institute of Science
The molecular mechanism of a diabetes vaccine revealed A team
of researchers led by Prof. Irun Cohen of the Weizmann
Institute of Science Immunology Department has revealed the
molecular mechanism of a vaccine for Type 1 diabetes. The new
findings should help amplify the effectiveness of the vaccine,
which is currently in advanced stages of clinical trials. Type
1 diabetes is an autoimmune disorder in which the immune
system mistakenly attacks the body's own insulin-producing
pancreatic cells, reducing and ultimately eliminating the
production of insulin - a hormone needed to convert sugar,
starches, and other foods into energy. Several years ago,
Prof. Cohen and colleagues developed a vaccine that arrests
the progression of Type 1 diabetes in laboratory animals. They
had discovered that a particular protein called HSP60, or even
only a small particular fragment of it - the peptide
designated p277 - is able to shut down the autoimmune response
causing this disorder. The vaccine is currently being tested
in clinical trials in Europe and the United States, but its
precise mechanism has until now been unknown.
"When translating these findings into a practical vaccine, we
knew enough about the mechanism to understand that this
protein is able to cause a decrease in the immune response,
but how it actually works eluded us," says Cohen. In a paper
published in the Journal of Clinical Investigation, the
scientists have managed to identify the exact immune cells
that p277 acts upon and its mechanism of action.
Autoimmune diseases occur when certain T cells in the immune
system attack the body's own cells and tissues. The scientists
discovered that p277 directs the activity of the immune system
in two ways. First, the p277 peptide steps up the activities
of a different type of T cell that regulates the amount of
potentially harmful T cells available. In addition, T cells
treated with p277 cause the delinquent T cells to secrete
anti-inflammatory substances instead of the
inflammation-causing ones that they usually make which lead to
autoimmune disease. This double action of the peptide weakens
the damaging activities of the immune response further. The
scientists also showed that in order to activate this
response, p277 must be bound to the receptor TLR-2, which is
found on the cell walls of the regulatory T cells.
"These findings are important, as it means that by
identifying the molecular activity of p277 with such
precision, we can copy nature's own system in regulating the
immune system and therefore, help to boost the immune system
in preventing the destruction of insulin-producing pancreatic
cells," says Cohen.
Postdoctoral fellow Dr. Alexandra Zanin-Zhorov spearheaded the
project; the other scientists participating in this study
were: the late Prof. Ofer Lider, Dr. Liora Cahalon,
postdoctoral fellow Guy Tal, and Raanan Margalit.
###
Prof. Irun Cohen's research is supported by the Minna James
Heineman Stiftung; and the Robert Koch Minerva Center for
Research in Autoimmune Disease.
Prof. Cohen is the incumbent of the Helen and Morris
Mauerberger Professorial Chair in Immunology.
--------------------------------------------------------------
-------------------
J Biol Chem. 2002 Nov 15;277(46):44531-8. Epub 2002 Aug 27.
Related Articles, Links
Mitochondrial Hsp60, resistance to oxidative stress, and the
labile iron pool are closely connected in Saccharomyces
cerevisiae.
Cabiscol E, Belli G, Tamarit J, Echave P, Herrero E, Ros J.
Departament de Ciencies Mediques Basiques, Facultat de
Medicina, Universitat de Lleida, Spain.
In the present study, we have analyzed the role of the
molecular chaperone Hsp60 in protection of Saccharomyces
cerevisiae against oxidative damage. We constructed mutant
strains in which the levels of Hsp60 protein, compared with
wild-type cells, were four times greater, and the addition of
doxycycline gradually reduces them to 20% of wild-type. Under
oxidative-stress conditions, the progressive decrease in Hsp60
levels in these mutants resulted in reduced cell viability and
an increase in both cell peroxide species and protein carbonyl
content. Protection of Fe/S-containing enzymes from oxidative
inactivation was found to be dose-dependent with respect to
Hsp60 levels. As these enzymes release their iron ions under
oxidative-stress conditions, the intracellular labile iron
pool, monitored with calcein, was higher in cells with reduced
Hsp60 levels. Consistently, the iron chelator deferoxamine
protected low Hsp60-expressing cells from both oxidant-induced
death and protein oxidation. These results indicate that the
role of Hsp60 in oxidative-stress defense is explained by
protection of several Fe/S proteins, which prevent the release
of iron ions and thereby avert further damage.
PMID: 12200437 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
-------------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
causing this disorder <<snip>> <<snip>> Hsp60 prevents the
release of iron ions <<snip>>
Public release date: 19-Jun-2006
Contact: Jennifer Manning jennifer@acwis.org 212-895-7952
American Committee for the Weizmann Institute of Science
The molecular mechanism of a diabetes vaccine revealed A team
of researchers led by Prof. Irun Cohen of the Weizmann
Institute of Science Immunology Department has revealed the
molecular mechanism of a vaccine for Type 1 diabetes. The new
findings should help amplify the effectiveness of the vaccine,
which is currently in advanced stages of clinical trials. Type
1 diabetes is an autoimmune disorder in which the immune
system mistakenly attacks the body's own insulin-producing
pancreatic cells, reducing and ultimately eliminating the
production of insulin - a hormone needed to convert sugar,
starches, and other foods into energy. Several years ago,
Prof. Cohen and colleagues developed a vaccine that arrests
the progression of Type 1 diabetes in laboratory animals. They
had discovered that a particular protein called HSP60, or even
only a small particular fragment of it - the peptide
designated p277 - is able to shut down the autoimmune response
causing this disorder. The vaccine is currently being tested
in clinical trials in Europe and the United States, but its
precise mechanism has until now been unknown.
"When translating these findings into a practical vaccine, we
knew enough about the mechanism to understand that this
protein is able to cause a decrease in the immune response,
but how it actually works eluded us," says Cohen. In a paper
published in the Journal of Clinical Investigation, the
scientists have managed to identify the exact immune cells
that p277 acts upon and its mechanism of action.
Autoimmune diseases occur when certain T cells in the immune
system attack the body's own cells and tissues. The scientists
discovered that p277 directs the activity of the immune system
in two ways. First, the p277 peptide steps up the activities
of a different type of T cell that regulates the amount of
potentially harmful T cells available. In addition, T cells
treated with p277 cause the delinquent T cells to secrete
anti-inflammatory substances instead of the
inflammation-causing ones that they usually make which lead to
autoimmune disease. This double action of the peptide weakens
the damaging activities of the immune response further. The
scientists also showed that in order to activate this
response, p277 must be bound to the receptor TLR-2, which is
found on the cell walls of the regulatory T cells.
"These findings are important, as it means that by
identifying the molecular activity of p277 with such
precision, we can copy nature's own system in regulating the
immune system and therefore, help to boost the immune system
in preventing the destruction of insulin-producing pancreatic
cells," says Cohen.
Postdoctoral fellow Dr. Alexandra Zanin-Zhorov spearheaded the
project; the other scientists participating in this study
were: the late Prof. Ofer Lider, Dr. Liora Cahalon,
postdoctoral fellow Guy Tal, and Raanan Margalit.
###
Prof. Irun Cohen's research is supported by the Minna James
Heineman Stiftung; and the Robert Koch Minerva Center for
Research in Autoimmune Disease.
Prof. Cohen is the incumbent of the Helen and Morris
Mauerberger Professorial Chair in Immunology.
--------------------------------------------------------------
-------------------
J Biol Chem. 2002 Nov 15;277(46):44531-8. Epub 2002 Aug 27.
Related Articles, Links
Mitochondrial Hsp60, resistance to oxidative stress, and the
labile iron pool are closely connected in Saccharomyces
cerevisiae.
Cabiscol E, Belli G, Tamarit J, Echave P, Herrero E, Ros J.
Departament de Ciencies Mediques Basiques, Facultat de
Medicina, Universitat de Lleida, Spain.
In the present study, we have analyzed the role of the
molecular chaperone Hsp60 in protection of Saccharomyces
cerevisiae against oxidative damage. We constructed mutant
strains in which the levels of Hsp60 protein, compared with
wild-type cells, were four times greater, and the addition of
doxycycline gradually reduces them to 20% of wild-type. Under
oxidative-stress conditions, the progressive decrease in Hsp60
levels in these mutants resulted in reduced cell viability and
an increase in both cell peroxide species and protein carbonyl
content. Protection of Fe/S-containing enzymes from oxidative
inactivation was found to be dose-dependent with respect to
Hsp60 levels. As these enzymes release their iron ions under
oxidative-stress conditions, the intracellular labile iron
pool, monitored with calcein, was higher in cells with reduced
Hsp60 levels. Consistently, the iron chelator deferoxamine
protected low Hsp60-expressing cells from both oxidant-induced
death and protein oxidation. These results indicate that the
role of Hsp60 in oxidative-stress defense is explained by
protection of several Fe/S proteins, which prevent the release
of iron ions and thereby avert further damage.
PMID: 12200437 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
-------------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk