Depletion of glutathione attenuates response of bone marrow stem cells to stromal cell-derived factor -1 [2007](IR91)

Depletion of glutathione attenuates response of bone marrow stem cells to stromal cell-derived factor -1 [2007](IR91)BK

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(Memo Item created on December 25, 2010 11:26 PM)
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Depletion of glutathione attenuates response of bone marrow stem cells to stromal cell-derived factor -1

http://www.fasebj.org/cgi/content/meeting_abstract/21/6/A737-b
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FASEB J.
April 2007
21 (Meeting Abstract Supplement) A737

(The FASEB Journal. 2007;21:702.12)
© 2007 FASEB
702.12
Depletion of glutathione attenuates response of bone marrow stem cells to stromal cell-derived factor -1
Smita Swaminathan Iyer1, Jianguo Xu2, Dean P Jones2, Kenneth Brigham2 and Mauricio Rojas2
1 Nutrition and Health Sciences Program, Emory University, 615,Michael Street, 215 Whitehead Bldg, Emory University, Atlanta, GA, 30322,
2 Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, Emory University, 615,Michael Street, 205,Whitehead Bldg, Emory University, Atlanta, GA, 30322

ABSTRACT

In adult organisms, stem cells, found primarily in the bone marrow and in low numbers in other organs, are mobilized to the injured tissue where they participate in the repair process. Stromal cell-derived factor -1a (SDF-1a) is critical for stem cell trafficking during injury. Very little is known about how nutrition affects this process. Our objectives were to determine how Glutathione (GSH) depletion, observed with aging and in numerous chronic disease states, affects the functional response of bone marrow cells to SDF-1a.

Bone marrow stem cells (BMSC) from 8 week old C57BL/6J mice were isolated, and were cultured for 24 hours in buthionine sulfoximine (BSO), an inhibitor of GSH synthesis. SDF-1a (120 ng/ml) dependent chemotaxis was determined in viable cells, over 3 hours, using a modified Boyden chamber method. We found a 5 fold decline in migration, in cells depleted of GSH compared to control.

Our data show that GSH is important in the directional migration of BMSC to SDF-1a and indicate that signal transduction pathways initiated by SDF-1a may be redox sensitive. Therefore, in states of chronic oxidative imbalance, stem cell response to SDF-1a may be attenuated slowing tissue regeneration and repair. As nutrition can impact levels of GSH, dietary control of antioxidant status may provide an opportunity to enhance repair and improve recovery in patients with injury.

Classifications
Cellular Mechanisms of Nutritional Modulation in Immunity
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The role of glutathione in radiation and drug induced cytotoxicity. [1987](IR91){These studies demonstrate that GSH modulation may have a major impact on the cytotoxicity of redox active drugs}.png

December 23, 2010; 06:11:10 p.m. Taipei Time

The role of glutathione in radiation and drug induced cytotoxicity. [1987](IR91).png

The role of glutathione in radiation and drug induced cytotoxicity. [1987](IR91){Diagrammatic representation of the inter-relationship of GSH with other cellular systems.}.png

The role of glutathione in radiation and drug induced cytotoxicity. [1987](IR91){These studies demonstrate that GSH modulation may have a major impact on the cytotoxicity of redox active drugs}.png

Keywords:

Clock, Watch, GSH, glutathione, interaction, mechanism, intricacy, 錯綜複雜的事物（或細節）

Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2 [2010[(IR91)

Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2 [2010[(IR91)

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(Memo Item created on December 16, 2010 07:55 PM)
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Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2

http://www.jbc.org/content/285/22/16582
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First Published on March 23, 2010, doi: 10.1074/jbc.M109.090506
May 28, 2010 The Journal of Biological Chemistry, 285, 16582-16587.

Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2 *
Heather M. Brechbuhl‡, Neal Gould§, Remy Kachadourian¶, Wayne R. Riekhof¶, Dennis R. Voelker¶ and Brian J. Day§¶‖**,1
- Author Affiliations

From the Departments of ‖Medicine,
**Immunology, and
§Pharmaceutical Sciences, University of Colorado Denver Health Sciences Center, Aurora, Colorado 80045 and
the Departments of ¶Medicine and
‡Pediatrics, National Jewish Health, Denver, Colorado 80206
1 To whom correspondence should be addressed: National Jewish Health, 1400 Jackson St., Denver, CO 80206. Tel.: 303-398-1121; Fax: 303-270-2263; E-mail: dayb@njhealth.org.
Abstract

Glutathione (GSH) transport is vital for maintenance of intracellular and extracellular redox balance. Only a few human proteins have been identified as transporters of GSH, glutathione disulfide (GSSG) and/or GSH conjugates (GS-X). Human epithelial MDA1586, A549, H1975, H460, HN4, and H157 cell lines were exposed to 2′,5′-dihydroxychalcone, which induces a GSH efflux response. A real-time gene superarray for 84 proteins found in families that have a known role in GSH, GSSG, and/or GS-X transport was employed to help identify potential GSH transporters. ABCG2 was identified as the only gene in the array that closely corresponded with the magnitude of 2′,5′-dihydroxychalcone (2′,5′-DHC)-induced GSH efflux. The role of human ABCG2 as a novel GSH transporter was verified in a Saccharomyces cerevisiae galactose-inducible gene expression system. Yeast expressing human ABCG2 had 2.5-fold more extracellular GSH compared with those not expressing ABCG2. GSH efflux in ABCG2-expressing yeast was abolished by the ABCG2 substrate methotrexate (10 μM), indicating competitive inhibition. In contrast, 2′,5′-DHC treatment of ABCG2-expressing yeast increased extracellular GSH levels in a dose-dependent manner with a maximum 3.5-fold increase in GSH after 24 h. In addition, suppression of ABCG2 with short hairpin RNA or ABCG2 overexpression in human epithelial cells decreased or increased extracellular GSH levels, respectively. Our data indicate that ABCG2 is a novel GSH transporter.

ABC Transporter Antioxidant Membrane Proteins Transport Amino Acids Yeast Glutathione
Footnotes

↵* This work was supported, in whole or in part, by National Institutes of Health Grants R01 HL084469 (to B. J. D.), R01 HL075523 (to B. J. D), R01 ES0175825, R37-GM32453 (to D. R. V), and 1F32-GM076798 (to W. R. R.). This work was also supported by American Cancer Society Great-West Division Postdoctoral Fellowship Award PF-06-288-01-CSM (to W. R. R.).

↵ The on-line version of this article (available at http://www.jbc.org) contains supplemental Experimental Procedures and additional references, Figs. 1–5, and Table 1.

Received December 2, 2009.
Revision received March 23, 2010.
© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
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ABCG2: structure, function and role in drug response. [2008](IR91)

ABCG2: structure, function and role in drug response. [2008](IR91)

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(Memo Item created on December 16, 2010 10:48 PM)
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ABCG2: structure, function and role in drug response.

http://www.ncbi.nlm.nih.gov/pubmed/18370855
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Expert Opin Drug Metab Toxicol. 2008 Jan;4(1):1-15.
ABCG2: structure, function and role in drug response.
Polgar O, Robey RW, Bates SE.
National Cancer Institute, Medical Oncology Branch, Center for Cancer Research, NIH, 9000 Rockville Pike, Building 10, Room 13N240, Bethesda, MD 20892, USA.

Abstract
ABCG2 was discovered in multi-drug-resistant cancer cells, with the identification of chemotherapeutic agents, such as mitoxantrone, flavopiridol, methotrexate and irinotecan as substrates. Later, drugs from other therapeutic groups were also described as substrates, including antibiotics, antivirals, HMG-CoA reductase inhibitors and flavonoids. An expanding list of compounds inhibiting ABCG2 has also been generated. The wide variety of drugs transported by ABCG2 and its normal tissue distribution with highest levels in the placenta (胎盤), intestine and liver, suggest a role in protection against xenobiotics. ABCG2 also has an important role in the pharmacokinetics (藥物動力學) of its substrates. Single nucleotide polymorphisms of the gene were shown to alter either plasma concentrations of substrate drugs or levels of resistance against chemotherapeutic agents in cell lines. ABCG2 was also described as the determinant of the side population of stem cells. All these aspects of the transporter warrant further research aimed at understanding ABCG2's structure, function and regulation of expression.

PMID: 18370855 [PubMed - indexed for MEDLINE]
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(Memo Item created on December 16, 2010 10:51 PM)
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Common added by WeiJin Tang (湯偉晉)
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Known GSH transporter
Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2

ABCG2 is a GSH transporter

Source; URL of the source or Name of the professional paper:
Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2 [2010[(IR91)
http://www.jbc.org/content/285/22/16582
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(Memo Item created on December 16, 2010 10:56 PM)
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Auxiliary info for understanding this paper
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Pharmacokinetics
藥物動力學
pharmacokinetics (藥物動力學)

The branch of pharmacology concerned with the movement of drugs within the body.

The study of the action of drugs in the body: method and rate of excretion; duration of effect; etc.
Source:
wordnetweb.princeton.edu/perl/webwn

large intestine
大腸
small intestine
小腸
intestine
腸子

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