Glucose transport and apoptosis
The transport and metabolism of glucose modify programmed cell death in a number of different cell types. This review presents three cell death paradigms that link a decrease in glucose transport to apoptosis. Although these pathways overlap, the glucose-dependent stimuli that trigger cell death differ. These paradigms include glucose deprivation-induced ATP depletion and stimulation of the mitochondrial death pathway cascade; glucose deprivation-induced oxidative stress and triggering of Bax-associated events including the JNK/MAPK signalling pathways; and finally hypoglycemia-regulated expression of HIF-1α, stabilization of p53 leading to an increase in p53-associated apoptosis. Several examples of each paradigm are presented. Future studies of glucose transport-associated apoptotic events will allow better understanding of the role of cellular metabolism in programmed cell death.
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- 1.Berridge MV, Tan AS, McCoy KD, Kansara M, Rudert F. CD95 (Fas/Apo-1)-induced Apoptosis results in loss of glucose transporter function. J Immunology 1996; 156: 4092–4099.Google Scholar
- 4.Johnson EM, Deckwerth TL, Deshmukh M. Neuronal death in developmental models: possible implications in neuropathy. Brain Path 1996; 6: 397–409.Google Scholar
- 13.Mark RJ, Pang Z, Geddes JW, Uchida K, Mattson MP. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons-involvement of membrane lipid peroxidation. J Neuroscience 1997; 17: 1046–1054.Google Scholar
- 15.Keller JN, Pang Z, Geddes JW, Begley JG, Germeyer A, Waeg G, Mattson MP. Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4–hydroxynonenal. J Neurochem1997; 69: 273–284.PubMedGoogle Scholar
- 17.PedersenWA, Cashman NR, Mattson MP. The lipid peroxidation product 4–hydroxynonenal impairs glutamate and glucose transport and choline acetyltransferase activity in NSC-19 motor neuron cells. Exp Neurology 1999; 155: 1–10.Google Scholar
- 18.Kostic V, Jackson-Lewis V, de Bilbao F, Dubois-Daupin M, Przedborski S. Bcl-2: Prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 1997; 277: 559–562.Google Scholar
- 27.Greenlund LJS, Deckwerth TL, Johnson EM Jr. Superoxide dismutase delays neuronal apoptosis: a role for reactive oxygen species in programmed neuronal death. Neuron 1995; 14: 303–315.Google Scholar
- 28.Carmeliet P, Dor Y, Herbert J-M, Fukkumura D, Brusselmans K, Dewerchin M, et al. Role of HIF-1 in hypoxia-mediated apoptosis, cell proliferation and tumor angiogenesis. Nature 1998; 394: 485–490.Google Scholar