TY - JOUR
T1 - Activation of glycolysis and apoptosis in glycogen storage disease type Ia
AU - Sun, Baodong
AU - Li, Songtao
AU - Yang, Liu
AU - Damodaran, Tirupapuliyur
AU - Desai, Dev
AU - Diehl, Anna Mae
AU - Alzate, Oscar
AU - Koeberl, Dwight D.
N1 - Funding Information:
We wish to acknowledge technical support from Ms. Zoie, E. Holzknecht and Mr. Andrew Bird. DDK was supported by the Children’s Fund for GSD Research, the Association for Glycogen Storage Disease, and the Duke Children’s Miracle Network. We deeply appreciate the dedication shown by Duke Vivarium, when caring for the G6Pase (−/−) mice. G6Pase (+/−) mice were kindly provided by Dr. Janice Chou at the National Institutes of Health. We thank Dr. Y.-T. Chen and Dr. Priya Kishnani for inspiration and support.
PY - 2009/8
Y1 - 2009/8
N2 - The deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage disease type Ia (GSD-Ia, von Gierke disease; MIM 232200), an autosomal recessive disorder of metabolism associated with life-threatening hypoglycemia, growth retardation, renal failure, hepatic adenomas, and hepatocellular carcinoma. Liver involvement includes the massive accumulation of glycogen and lipids due to accumulated glucose-6-phosphate and glycolytic intermediates. Proteomic analysis revealed elevations in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and other enzymes involved in glycolysis. GAPDH was markedly increased in murine G6Pase-deficient hepatocytes. The moonlighting role of GAPDH includes increasing apoptosis, which was demonstrated by increased TUNEL assay positivity and caspase 3 activation in the murine GSD-Ia liver. These analyses of hepatic involvement in GSD-Ia mice have implicated the induction of apoptosis in the pathobiology of GSD-Ia.
AB - The deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage disease type Ia (GSD-Ia, von Gierke disease; MIM 232200), an autosomal recessive disorder of metabolism associated with life-threatening hypoglycemia, growth retardation, renal failure, hepatic adenomas, and hepatocellular carcinoma. Liver involvement includes the massive accumulation of glycogen and lipids due to accumulated glucose-6-phosphate and glycolytic intermediates. Proteomic analysis revealed elevations in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and other enzymes involved in glycolysis. GAPDH was markedly increased in murine G6Pase-deficient hepatocytes. The moonlighting role of GAPDH includes increasing apoptosis, which was demonstrated by increased TUNEL assay positivity and caspase 3 activation in the murine GSD-Ia liver. These analyses of hepatic involvement in GSD-Ia mice have implicated the induction of apoptosis in the pathobiology of GSD-Ia.
KW - Apoptosis
KW - Fatty liver
KW - Gene therapy
KW - Glucose-6-phosphatase
KW - Glyceraldehyde-3-phosphate dehydrogenase
KW - Glycogen storage disease
KW - Inherited disorder of metabolism
KW - von Gierke disease
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U2 - 10.1016/j.ymgme.2009.04.003
DO - 10.1016/j.ymgme.2009.04.003
M3 - Article
C2 - 19419892
AN - SCOPUS:67649668963
SN - 1096-7192
VL - 97
SP - 267
EP - 271
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 4
ER -