Glyceraldehyde-3-phosphate dehydrogenase exerts different biologic activities in apoptotic and proliferating hepatocytes according to its subcellular localization |
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Authors: | Luciana Barbini Joaquin Rodríguez Fernando Dominguez Felix Vega |
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Institution: | (1) Departamento de Fisiologia, Facultad de Veterinaria, Lugo, Spain;(2) Departamento de Farmacologia, Facultad de Ciencias Bioquímicas y Farmaceuticas, Universidad Nacional de Rosario, Rosario, Argentina;(3) Laboratorios de Neurociencia “Ramon Dominguez”, Departamento de Fisiologia, Facultad de Medicina, Universidad de Santiago de Compostela, Santiago de Compostela, Spain;(4) Departamento de Fisiologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain |
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Abstract: | Recent evidences indicate new roles for the glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in essential
mammalian cell processes, such as apoptosis and proliferation. To clarify the involvement of this protein in growth and programmed
cell death in the liver, cell models of hepatocytes in culture were used to study GAPDH expression, localization and enzymatic
activity in hepatocyte proliferation and apoptosis. GAPDH expression in cell compartments was studied by Western blot. Nuclear
expression of GAPDH increased in apoptosis, and cytoplasmic expression was elevated in apoptosis and proliferation. Subcellular
localization was determined by GAPDH immunostaining and confocal microscopic analysis. Quiescent and proliferating hepatocytes
showed cytoplasmic GAPDH, while apoptotic cells showed cytoplasmic but also some nuclear staining. The glycolytic activity
of GAPDH was studied in nuclear and cytoplasmic cell compartments. GAPDH enzymatic activity increased in the nucleus of apoptotic
cells and in cytoplasms of apoptotic and proliferating hepatocytes. Our observations indicate that during hepatocyte apoptosis
GAPDH translocates to the nucleus, maintaining in part its dehydrogenase activity, and suggest that this translocation may
play a role in programmed hepatocyte death. GAPDH over-expression and the increased enzymatic activity in proliferating cells,
with preservation of its cytoplasmic localization, would occur in response to the elevated energy requirements of dividing
hepatocytes. In conclusion, GAPDH plays different roles or biological activities in proliferating and apoptotic hepatocytes,
according to its subcellular localization. |
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Keywords: | glyceraldehyde-3-phosphate dehydrogenase hepatocyte apoptosis proliferation glycolytic activity |
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