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2019-01-28
The mitochondrion： a central architect
of copper homeostasis. [2017];_WJD_2019-0128_V001R01_IR94_
Source (資訊來源):
https://www.ncbi.nlm.nih.gov/pubmed/28952650
Info cited on 2019-01-28-WD1 (資訊引用於 中華民國108年1月28日) by 湯偉晉 (WeiJin Tang)
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Metallomics. 2017 Nov 15;9(11):1501-1512. doi: 10.1039/c7mt00221a.
The mitochondrion: a central architect of copper homeostasis.
The mitochondrion: a
central architect of copper homeostasis.
The mitochondrion: a central architect of copper homeostasis.
Baker ZN1, Cobine PA, Leary SC.
Author information
1
Department of Biochemistry, University of Saskatchewan, Saskatoon, SK S7N 5E5,
Canada.
Abstract
All known eukaryotes require copper for their development and survival. The
essentiality of copper reflects its widespread use as a co-factor in conserved
enzymes that catalyze biochemical reactions critical to energy production, free
radical detoxification, collagen deposition, neurotransmitter biosynthesis and
iron homeostasis. However, the
prioritized use of copper poses an organism with a considerable challenge
because, in its unbound form, copper can potentiate free radical production and
displace iron-sulphur clusters to disrupt protein function. Protective
mechanisms therefore evolved to mitigate this challenge and tightly regulate
the acquisition, trafficking and storage of copper such that the metal ion is rarely found in its free
form in the cell. Findings by a number of groups over the last ten years
emphasize that this regulatory
framework forms the foundation of a system that is capable of monitoring copper
status and reprioritizing copper usage at both the cellular and systemic levels
of organization. While the identification of relevant molecular
mechanisms and signaling pathways has proven to be difficult and remains a
barrier to our full understanding of the regulation of copper homeostasis, mounting evidence points to the
mitochondrion as a pivotal hub in this regard in both healthy and diseased
states. Here, we review our current understanding of copper handling
pathways contained within the organelle and consider plausible mechanisms that
may serve to functionally couple their activity to that of other cellular copper handling machinery to
maintain copper homeostasis.
PMID: 28952650 PMCID: PMC5688007 DOI: 10.1039/c7mt00221a
[Indexed for MEDLINE] Free PMC Article
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2019年1月28日 星期一
2019年1月15日 星期二
Glutathione, a first line of defense against cadmium toxicity. [1987]; Meister, Cornell University;_WJD_2019-0115_V001R01_IR94_
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2019-01-15
Glutathione, a first line of defense against cadmium toxicity. [1987]; Meister, Cornell University;_WJD_2019-0115_V001R01_IR94_
Source (資訊來源):
https://www.ncbi.nlm.nih.gov/pubmed/2887478
Info cited on 2019-01-15-WD2 (資訊引用於 中華民國108年1月15日) by 湯偉晉 (WeiJin Tang)
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FASEB J. 1987 Sep;1(3):220-3.
Glutathione, a first line of defense against cadmium toxicity.
Glutathione, a first line of defense against cadmium toxicity.
Glutathione, a first line of defense against cadmium toxicity.
Singhal RK, Anderson ME, Meister A.
Abstract
Experimental modulation of cellular glutathione levels has been used to explore the role of glutathione in cadmium toxicity. Mice treated with buthionine sulfoximine [an effective irreversible inhibitor of gamma-glutamylcysteine synthetase (EC 6.3.2.2) that decreases cellular levels of glutathione markedly] were sensitized to the toxic effects of CdCl2. Mice pretreated with a sublethal dose of Cd2+ to induce metallothionein synthesis were not sensitized to Cd2+ by buthionine sulfoximine. Mice sensitized to Cd2+ by buthionine sulfoximine were protected against a lethal dose of Cd2+ by glutathione mono isopropyl ester (L-gamma-glutamyl-L-cysteinylglycylisopropyl ester), but not by glutathione. These results are in accord with studies that showed that glutathione mono esters (in contrast to glutathione) are efficiently transported into cells and converted intracellularly to glutathione. The findings indicate that intracellular glutathione functions in protection against Cd2+ toxicity, and that this tripeptide provides a first line of defense against Cd2+ before induction of metallothionein synthesis occurs. The experimental approach used here in which cellular levels of glutathione are decreased or increased seems applicable to investigation of other types of metal toxicity and of other glutathione-dependent biological phenomena.
PMID: 2887478
[Indexed for MEDLINE]
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2019-01-15
Glutathione, a first line of defense against cadmium toxicity. [1987]; Meister, Cornell University;_WJD_2019-0115_V001R01_IR94_
Source (資訊來源):
https://www.ncbi.nlm.nih.gov/pubmed/2887478
Info cited on 2019-01-15-WD2 (資訊引用於 中華民國108年1月15日) by 湯偉晉 (WeiJin Tang)
#
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FASEB J. 1987 Sep;1(3):220-3.
Glutathione, a first line of defense against cadmium toxicity.
Glutathione, a first line of defense against cadmium toxicity.
Glutathione, a first line of defense against cadmium toxicity.
Singhal RK, Anderson ME, Meister A.
Abstract
Experimental modulation of cellular glutathione levels has been used to explore the role of glutathione in cadmium toxicity. Mice treated with buthionine sulfoximine [an effective irreversible inhibitor of gamma-glutamylcysteine synthetase (EC 6.3.2.2) that decreases cellular levels of glutathione markedly] were sensitized to the toxic effects of CdCl2. Mice pretreated with a sublethal dose of Cd2+ to induce metallothionein synthesis were not sensitized to Cd2+ by buthionine sulfoximine. Mice sensitized to Cd2+ by buthionine sulfoximine were protected against a lethal dose of Cd2+ by glutathione mono isopropyl ester (L-gamma-glutamyl-L-cysteinylglycylisopropyl ester), but not by glutathione. These results are in accord with studies that showed that glutathione mono esters (in contrast to glutathione) are efficiently transported into cells and converted intracellularly to glutathione. The findings indicate that intracellular glutathione functions in protection against Cd2+ toxicity, and that this tripeptide provides a first line of defense against Cd2+ before induction of metallothionein synthesis occurs. The experimental approach used here in which cellular levels of glutathione are decreased or increased seems applicable to investigation of other types of metal toxicity and of other glutathione-dependent biological phenomena.
PMID: 2887478
[Indexed for MEDLINE]
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Cysteine／Glutathione Deficiency： A Significant and Treatable Corollary of Disease; In book： The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine; Stanford University [2019];_WJD_2019-0115_V001R01_IR94_
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2019-01-15
Cysteine／Glutathione Deficiency： A Significant and Treatable Corollary of Disease; In book： The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine; Stanford University [2019];_WJD_2019-0115_V001R01_IR94_
Source (資訊來源):
https://www.researchgate.net/publication/327799571_CysteineGlutathione_Deficiency_A_Significant_and_Treatable_Corollary_of_Disease
Info cited on 2019-01-15-WD2 (資訊引用於 中華民國108年1月15日) by 湯偉晉 (WeiJin Tang)
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Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease
Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease
Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease
Chapter (PDF Available) · January 2019 with 241 Reads
DOI: 10.1007/978-981-10-5311-5_20
In book: The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine, pp.349-386
Cite this publication
Abstract
Glutathione (GSH) deficiency may play a pivotal role in a variety of apparently unrelated clinical conditions and diseases. Orally administered N-acetylcysteine (NAC), which replenishes the cysteine required for GSH synthesis, has been tested in a large number of randomized placebo-controlled trials involving these diseases and conditions. This chapter focused on developing a base of evidence suggesting that NAC administration improves disease by increasing cysteine and/or GSH in a variety of diseases, thereby implying a significant role for GSH deficiency in the clinical basis of many diseases. To develop this base of evidence, we systematically selected studies which considered the hypothesis that the therapeutic efficacy for NAC is an indication that cysteine and/or GSH deficiency is a pathophysiological part of the diseases studied. In this manner we focus this chapter on explaining the biological mechanisms of NAC therapy in a wide variety of disorders and demonstrate its ubiquitous role in improving disease that involves disrupted GSH and/or cysteine metabolism.
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2019-01-15
Cysteine／Glutathione Deficiency： A Significant and Treatable Corollary of Disease; In book： The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine; Stanford University [2019];_WJD_2019-0115_V001R01_IR94_
Source (資訊來源):
https://www.researchgate.net/publication/327799571_CysteineGlutathione_Deficiency_A_Significant_and_Treatable_Corollary_of_Disease
Info cited on 2019-01-15-WD2 (資訊引用於 中華民國108年1月15日) by 湯偉晉 (WeiJin Tang)
#
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Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease
Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease
Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease
Chapter (PDF Available) · January 2019 with 241 Reads
DOI: 10.1007/978-981-10-5311-5_20
In book: The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine, pp.349-386
Cite this publication
Abstract
Glutathione (GSH) deficiency may play a pivotal role in a variety of apparently unrelated clinical conditions and diseases. Orally administered N-acetylcysteine (NAC), which replenishes the cysteine required for GSH synthesis, has been tested in a large number of randomized placebo-controlled trials involving these diseases and conditions. This chapter focused on developing a base of evidence suggesting that NAC administration improves disease by increasing cysteine and/or GSH in a variety of diseases, thereby implying a significant role for GSH deficiency in the clinical basis of many diseases. To develop this base of evidence, we systematically selected studies which considered the hypothesis that the therapeutic efficacy for NAC is an indication that cysteine and/or GSH deficiency is a pathophysiological part of the diseases studied. In this manner we focus this chapter on explaining the biological mechanisms of NAC therapy in a wide variety of disorders and demonstrate its ubiquitous role in improving disease that involves disrupted GSH and/or cysteine metabolism.
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Glutathione is required for intestinal function. [1990];_WJD_2019-0115_V001R01_IR94_
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2019-01-15
Glutathione is required for intestinal function. [1990];_WJD_2019-0115_V001R01_IR94_
Source (資訊來源):
https://www.ncbi.nlm.nih.gov/pubmed/2308931
Info cited on 2019-01-15-WD2 (資訊引用於 中華民國108年1月15日) by 湯偉晉 (WeiJin Tang)
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Send to
Proc Natl Acad Sci U S A. 1990 Mar;87(5):1715-9.
Glutathione is required for intestinal function.
Glutathione is required for intestinal function.
Glutathione is required for intestinal function.
Mårtensson J1, Jain A, Meister A.
Author information
1
Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
Abstract
Glutathione (GSH) deficiency produced in mice by giving buthionine sulfoximine leads to severe degeneration of the epithelial cells of the jejunum and colon. This is prevented by giving GSH monoester (orally or i.p.) and also by giving GSH (orally, but not i.p.). The i.p. administration leads to high plasma levels of GSH but does not appreciably increase GSH levels in intestinal mucosa or pancreas. These and previous studies on lens, lung, lymphocytes, liver, heart, and skeletal muscle indicate that there is very little, if any, transport of intact GSH from plasma to these tissues. Cells can use extracellular GSH by a pathway involving its cleavage, uptake of products and intracellular GSH synthesis. Epithelial cells of the gastrointestinal tract may use this pathway and can also take up lumenal GSH (which arises partly from the bile) by a mechanism(s) that may involve transport of dipeptides or of GSH. It is suggested that biliary GSH normally functions in the protection of intestinal mucosa. Administration of GSH may be protective of the gastrointestinal epithelium and may also serve as a good source of cysteine moieties for intracellular GSH synthesis in the gastrointestinal tract and in other tissues. Administration of GSH delivery agents such as GSH esters is more effective than administration of GSH in increasing cellular and mitochondrial levels of GSH.
PMID: 2308931 PMCID: PMC53553
[Indexed for MEDLINE] Free PMC Article
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2019-01-15
Glutathione is required for intestinal function. [1990];_WJD_2019-0115_V001R01_IR94_
Source (資訊來源):
https://www.ncbi.nlm.nih.gov/pubmed/2308931
Info cited on 2019-01-15-WD2 (資訊引用於 中華民國108年1月15日) by 湯偉晉 (WeiJin Tang)
#
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Send to
Proc Natl Acad Sci U S A. 1990 Mar;87(5):1715-9.
Glutathione is required for intestinal function.
Glutathione is required for intestinal function.
Glutathione is required for intestinal function.
Mårtensson J1, Jain A, Meister A.
Author information
1
Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
Abstract
Glutathione (GSH) deficiency produced in mice by giving buthionine sulfoximine leads to severe degeneration of the epithelial cells of the jejunum and colon. This is prevented by giving GSH monoester (orally or i.p.) and also by giving GSH (orally, but not i.p.). The i.p. administration leads to high plasma levels of GSH but does not appreciably increase GSH levels in intestinal mucosa or pancreas. These and previous studies on lens, lung, lymphocytes, liver, heart, and skeletal muscle indicate that there is very little, if any, transport of intact GSH from plasma to these tissues. Cells can use extracellular GSH by a pathway involving its cleavage, uptake of products and intracellular GSH synthesis. Epithelial cells of the gastrointestinal tract may use this pathway and can also take up lumenal GSH (which arises partly from the bile) by a mechanism(s) that may involve transport of dipeptides or of GSH. It is suggested that biliary GSH normally functions in the protection of intestinal mucosa. Administration of GSH may be protective of the gastrointestinal epithelium and may also serve as a good source of cysteine moieties for intracellular GSH synthesis in the gastrointestinal tract and in other tissues. Administration of GSH delivery agents such as GSH esters is more effective than administration of GSH in increasing cellular and mitochondrial levels of GSH.
PMID: 2308931 PMCID: PMC53553
[Indexed for MEDLINE] Free PMC Article
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Mitochondrial changes associated with glutathione deficiency. [1995]; Meister, Cornell University;_WJD_2019-0115_V001R01_IR94_
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2019-01-15
Mitochondrial changes associated with glutathione deficiency. [1995]; Meister, Cornell University;_WJD_2019-0115_V001R01_IR94_
Source (資訊來源):
https://www.ncbi.nlm.nih.gov/pubmed/7599223
Info cited on 2019-01-15-WD2 (資訊引用於 中華民國108年1月15日) by 湯偉晉 (WeiJin Tang)
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Biochim Biophys Acta. 1995 May 24;1271(1):35-42.
Mitochondrial changes associated with glutathione deficiency.
Mitochondrial changes associated with glutathione deficiency.
Mitochondrial changes associated with glutathione deficiency.
Meister A1.
Author information
1
Department of Biochemistry, Cornell University Medical College, New York, NY 10021, USA.
Abstract
Glutathione deficiency produced by giving buthionine sulfoximine (an inhibitor of gamma-glutamylcysteine synthetase) to animals, leads to biphasic decline in cellular glutathione levels associated with sequestration of glutathione in mitochondria. Liver mitochondria lack the enzymes needed for glutathione synthesis. Mitochondrial glutathione arises from the cytosol. Rat liver mitochondria have a multicomponent system (with Kms of approx. 60 microM and 5.4 mM) that underlies their remarkable ability to transport and retain glutathione. Mitochondria produce substantial quantities of reactive oxygen species; this is opposed by reactions involving glutathione. Glutathione deficiency leads to widespread mitochondrial damage which is lethal in newborn rats and guinea pigs, animals that do not synthesize ascorbate. Glutathione esters and ascorbate protect against the lethal and other effects of glutathione deficiency. Ascorbate spares glutathione; it increases mitochondrial glutathione in glutathione-deficient animals. Glutathione esters delay onset of scurvy in ascorbate-deficient guinea pigs; thus, glutathione spares ascorbate. Glutathione and ascorbate function together in protecting mitochondria from oxidative damage.
PMID: 7599223
[Indexed for MEDLINE] Free full text
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2019-01-15
Mitochondrial changes associated with glutathione deficiency. [1995]; Meister, Cornell University;_WJD_2019-0115_V001R01_IR94_
Source (資訊來源):
https://www.ncbi.nlm.nih.gov/pubmed/7599223
Info cited on 2019-01-15-WD2 (資訊引用於 中華民國108年1月15日) by 湯偉晉 (WeiJin Tang)
#
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Biochim Biophys Acta. 1995 May 24;1271(1):35-42.
Mitochondrial changes associated with glutathione deficiency.
Mitochondrial changes associated with glutathione deficiency.
Mitochondrial changes associated with glutathione deficiency.
Meister A1.
Author information
1
Department of Biochemistry, Cornell University Medical College, New York, NY 10021, USA.
Abstract
Glutathione deficiency produced by giving buthionine sulfoximine (an inhibitor of gamma-glutamylcysteine synthetase) to animals, leads to biphasic decline in cellular glutathione levels associated with sequestration of glutathione in mitochondria. Liver mitochondria lack the enzymes needed for glutathione synthesis. Mitochondrial glutathione arises from the cytosol. Rat liver mitochondria have a multicomponent system (with Kms of approx. 60 microM and 5.4 mM) that underlies their remarkable ability to transport and retain glutathione. Mitochondria produce substantial quantities of reactive oxygen species; this is opposed by reactions involving glutathione. Glutathione deficiency leads to widespread mitochondrial damage which is lethal in newborn rats and guinea pigs, animals that do not synthesize ascorbate. Glutathione esters and ascorbate protect against the lethal and other effects of glutathione deficiency. Ascorbate spares glutathione; it increases mitochondrial glutathione in glutathione-deficient animals. Glutathione esters delay onset of scurvy in ascorbate-deficient guinea pigs; thus, glutathione spares ascorbate. Glutathione and ascorbate function together in protecting mitochondria from oxidative damage.
[Indexed for MEDLINE] Free full text
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