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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5704-5711. Prepublished online as a Blood First Edition Paper on April 17, 2008; DOI 10.1182/blood-2007-12-129114. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-12-129114v1 111/12/5704    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kim, S. Y. Articles by Chou, J. Y. Search for Related Content PubMed PubMed Citation Articles by Kim, S. Y. Articles by Chou, J. Y. Related Collections Phagocytes Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Neutrophil stress and apoptosis underlie myeloid dysfunction in glycogen storage disease type Ib So Youn Kim1,*, Hyun Sik Jun1,*, Paul A. Mead1, Brian C. Mansfield1, and Janice Y. Chou1 1 Section on Cellular Differentiation, Heritable Disorders Branch, National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT) that works with a liver/kidney/intestine–restricted glucose-6-phosphatase- (G6Pase-) to maintain glucose homeostasis between meals. Clinically, GSD-Ib patients manifest disturbed glucose homeostasis and neutrophil dysfunctions but the cause of the latter is unclear. Neutrophils express the ubiquitously expressed G6PT and G6Pase-β that together transport G6P into the endoplasmic reticulum (ER) lumen and hydrolyze it to glucose. Because we expected G6PT-deficient neutrophils to be unable to produce endogenous glucose, we hypothesized this would lead to ER stress and increased apoptosis. Using GSD-Ib mice, we showed that GSD-Ib neutrophils exhibited increased production of ER chaperones and oxidative stress, consistent with ER stress, increased annexin V binding and caspase-3 activation, consistent with an increased rate of apoptosis. Bax activation, mitochondrial release of proapoptotic effectors, and caspase-9 activation demonstrated the involvement of the intrinsic mitochondrial pathway in these processes. The results demonstrate that G6P translocation and hydrolysis are required for normal neutrophil functions and support the hypothesis that neutrophil dysfunction in GSD-Ib is due, at least in part, to ER stress and increased apoptosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. M. Ravindranath, P. Y. Mong, R. Ananthakrishnan, Q. Li, N. Quadri, A. M. Schmidt, R. Ramasamy, and Q. Wang Novel Role for Aldose Reductase in Mediating Acute Inflammatory Responses in the Lung J. Immunol., December 15, 2009; 183(12): 8128 - 8137. [Abstract] [Full Text] [PDF]

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