Astroglial pentose phosphate pathway rates in response to high-glucose environments

ASN Neuro

Volumn 4, Issue 2, 2012, Pages 71-88

  Takahashi, Shinichi ^a   Izawa, Yoshikane ^a   Suzuki, Norihiro ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Astrocyte; Diabetes mellitus; ER (endoplasmic reticulum) stress; Glucose metabolism; Kelch like enoyl CoA hydratase associated protein 1 (keap1) nuclear factorerythroid 2 p45 subunit related factor 2 (Nrf2); Pentose phosphate pathway (PPP)

Indexed keywords

CARBON DIOXIDE; GLUCOSE; GLUCOSE 6 PHOSPHATE DEHYDROGENASE; GLUCOSE REGULATED PROTEIN 78; GLUTATHIONE; HEXOSAMINE; HYDROGEN PEROXIDE; PENTOSE PHOSPHATE; REACTIVE OXYGEN METABOLITE; TRANSCRIPTION FACTOR NRF2; ADVANCED GLYCATION END PRODUCT; CALCIUM; DEOXYGLUCOSE; HEAT SHOCK PROTEIN; HSPA5 PROTEIN, RAT; LYSINE; LYSYL ASPARTYL GLUTAMYL LEUCINE; LYSYL-ASPARTYL-GLUTAMYL-LEUCINE; OLIGOPEPTIDE; SIGNAL PEPTIDE;

ANIMAL CELL; ANTIOXIDANT ACTIVITY; ARTICLE; BRAIN PROTECTION; CARBON METABOLISM; CELL ACTIVATION; CELLULAR DISTRIBUTION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CULTURE MEDIUM; ENDOPLASMIC RETICULUM STRESS; ENVIRONMENTAL ENRICHMENT; GLUCOSE PHOSPHORYLATION; IMMUNOHISTOCHEMISTRY; MACROGLIA; NERVE CELL CULTURE; NONHUMAN; OXIDATIVE STRESS; PENTOSE PHOSPHATE CYCLE; PHOSPHORYLATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RAT; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; UPREGULATION; ANALYSIS OF VARIANCE; ANIMAL; ANIMAL EMBRYO; ASTROCYTE; BRAIN CORTEX; CELL CULTURE; CYTOLOGY; DOSE RESPONSE; DRUG EFFECT; FEMALE; METABOLISM; NERVE CELL; NEWBORN; OXIDATION REDUCTION REACTION; PREGNANCY; SPRAGUE DAWLEY RAT; TIME;

ANALYSIS OF VARIANCE; ANIMALS; ANIMALS, NEWBORN; ASTROCYTES; CALCIUM ISOTOPES; CELLS, CULTURED; CEREBRAL CORTEX; DEOXYGLUCOSE; DOSE-RESPONSE RELATIONSHIP, DRUG; EMBRYO, MAMMALIAN; FEMALE; GLUCOSE; GLUTATHIONE; GLYCOSYLATION END PRODUCTS, ADVANCED; HEAT-SHOCK PROTEINS; HYDROGEN PEROXIDE; LYSINE; NEURONS; NF-E2-RELATED FACTOR 2; OLIGOPEPTIDES; OXIDATION-REDUCTION; PENTOSE PHOSPHATE PATHWAY; PHOSPHORYLATION; PREGNANCY; PROTEIN SORTING SIGNALS; RATS; RATS, SPRAGUE-DAWLEY; REACTIVE OXYGEN SPECIES; TIME FACTORS;

EID: 84859013589     PISSN: None     EISSN: 17590914     Source Type: Journal    
DOI: 10.1042/AN20120002     Document Type: Article

References (98)

1. Abe T, Takahashi S, Suzuki N (2006a) Oxidative metabolism in cultured rat astroglia: effects of reducing the glucose concentration in the culture medium and of D-aspartate or potassium stimulation. J Cereb Blood Flow Metab 26:153-160.
2. Abe T, Takahashi S, Suzuki N (2006b) Metabolic properties of astrocytes differentiated from rat neurospheres. Brain Res 1101:5-11.
3. Alvarez E, Roncero I, Chowen JA, Vazquez P, Blazquez E (2002) Evidence that glucokinase regulatory protein is expressed and interacts with glucokinase in rat brain. J Neurochem 80:45-53.
4. Appel SH, Parrot BL (1970) Hexose monophosphate pathway in synapses. J Neurochem 17:1619-1626.
5. Asanuma M, Miyazaki I, Diaz Corrales FJ, Kimoto N, Kikkawa Y, Takeshima M, Miyoshi K, Murata M (2010) Neuroprotective effects of zonisamide target astrocyte. Ann Neurol 67:239-249.
6. 2+ levels. J Neurochem 109(Suppl. 1):87-93.
7. Ball KK, Harik L, Gandhi GK, Cruz NF, Dienel GA (2011) Reduced gap junctional communication among astrocytes in experimental diabetes: contributions of altered connexin protein levels and oxidative-nitrosative modifications. J Neurosci Res 89:2052-2067.
8. Ben Yoseph O, Boxer PA, Ross BD (1996a) Assessment of the role of the glutathione and pentose phosphate pathways in the protection of primary cerebrocortical cultures from oxidative stress. J Neurochem 66: 2329-2337.
9. Ben Yoseph O, Boxer PA, Ross BD (1996b) Noninvasive assessment of the relative roles of cerebral antioxidant enzymes by quantitation of pentose phosphate pathway activity. Neurochem Res 21:1005-1012.
10. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P (2006) Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 5:64-74.
11. Bloom DA (2003) Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element-mediated NAD(P)H:quinone oxidoreductase-1 gene expression. J Biol Chem 278:44675-44682.
12. Bolaños JP, Almeida A, Moncada S (2010) Glycolysis: a bioenergetic or a survival pathway? Trends Biochem Sci 35:145-149.
13. Bouzier Sore AK, Voisin P, Canioni P, Magistretti PJ, Pellerin L (2003) Lactate is a preferential oxidative energy substrate over glucose for neurons in culture. J Cereb Blood Flow Metab 23:1298-1306.
14. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813-820.
15. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615-1625.
16. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001) Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 32:2426-2432.
17. Cereda E, Barichella M, Pedrolli C, Klersy C, Cassani E, Caccialanza R, Pezzoli G (2011) Diabetes and risk of Parkinson's Disease: a systematic review and meta-analysis. Diabetes Care 34:2614-2623.
18. Chatterjee S, Noack H, Possel H, Keilhoff G, Wolf G (1999) Glutathione levels in primary glial cultures: monochlorobimane provides evidence of cell type-specific distribution. Glia 27:152-161.
19. Cheung KL, Kong AN (2010) Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS Journal 12:87-97.
20. Chih CP, Roberts EL Jr (2003) Energy substrates for neurons during neural activity: a critical review of the astrocyte-neuron lactate shuttle hypothesis. J Cereb Blood Flow Metab 23:1263-1281.
21. Chih CP, Lipton P, Roberts EL Jr (2001) Do active cerebral neurons really use lactate rather than glucose? Trends Neurosci 24:573-578.
22. Clarke DD, Sokoloff L (1999) Circulation and energy metabolism of the brain. In: Basic Neurochemistry: Molecular, Cellular, and Medical Aspects (Siegel G, Agranoff B, Albers RW, Fisher S, eds), 6th edn, pp. 637-669, Lippincott-Raven, Philadelphia.
23. Contreras L, Satrustegui J (2009) Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways. J Biol Chem 284:7091-7099.
24. Cox DJ, Kovatchev BP, Gonder-Frederick LA, Summers KH, McCall A, Grimm KJ, Clarke WL (2005) Relationships between hyperglycemia and cognitive performance among adults with type 1 and type 2 diabetes. Diabetes Care 28:71-77.
25. Cullinan SB (2004) PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem 279:20108-20117.
26. Cullinan SB, Diehl J (2006) Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol 38:317-332.
27. Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA (2003) Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol 23:7198-7209.
28. Danilov CA, Chandrasekaran K, Racz J, Soane L, Zielke C, Fiskum G (2009) Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation. Glia 57:645-656.
29. Delgado-Esteban M, Almeida A, Bolaños JP (2000) D-Glucose prevents glutathione oxidation and mitochondrial damage after glutamate receptor stimulation in rat cortical primary neurons. J Neurochem 75: 1618-1624.
30. Dhar A, Desai K, Kazachmov M, Yu P, Wu L (2008) Methylglyoxal production in vascular smooth muscle cells from different metabolic precursors. Metabolism Clin Exp 57:1211-1220.
31. Dienel GA (2009) Energy metabolism in the brain. In: From Molecules to Networks: an Introduction to Cellular and Molecular Neuroscience (Byrne JH, Roberts JL, eds), 2nd edn, pp. 49-110, Academic Press, London.
32. Dienel GA, Cruz NF (2004) Nutrition during brain activation: does cell-to-cell lactate shuttling contribute significantly to sweet and sour food for thought? Neurochem Int 45:321-351.
33. Dienel GA, Hertz L (2005) Astrocytic contributions to bioenergetics of cerebral ischemia. Glia 50:362-388.
34. Dienel GA, Cruz NF, Mori K, Holden JE, Sokoloff L (1991) Direct measurement of the lambda of the lumped constant of the deoxyglucose method in rat brain: determination of lambda and lumped constant from tissue glucose concentration or equilibrium brain/plasma distribution ratio for methylglucose. J Cereb Blood Flow Metab 11:25-34.
35. DiNuzzo M, Mangia S, Maraviglia B, Giove F (2009) Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics: evidence from mathematical modeling. J Cereb Blood Flow Metab 30:586-602.
36. Dringen R, Hoepken H, Minich T, Ruedig C (2007) Pentose phosphate pathway and NADPH metabolism. In: Brain Energetics. Integration of Molecular and Cellular Processes (Gibson GE and Dienel GA, eds.) Handbook of Neurochemistry and Molecular Biology, 3rd edn (Lajtha A, series ed.), pp. 41-62. Springer-Verlag, Berlin.
37. Fowler GC, Vasudevan DA (2010) Type 2 diabetes mellitus: managing hemoglobin A(1c) and beyond. South Med J 103:911-916.
38. Fox PT, Raichle ME (1986) Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci USA 83:1140-1144.
39. Fox PT, Raichle ME, Mintun MA, Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462-464.
40. Gandhi GK, Ball KK, Cruz NF, Dienel GA (2010) Hyperglycaemia and diabetes impair gap junctional communication among astrocytes. ASN NEURO 2:e00030. doi:10.1042/AN20090048.
41. García Nogales P, Almeida A, Bolaños JP (2003) Peroxynitrite protects neurons against nitric oxide-mediated apoptosis. A key role for glucose-6-phosphate dehydrogenase activity in neuroprotection. J Biol Chem 278:864-874.
42. Gomes A, Fernandes E, Lima JL (2005) Fluorescence probes used for detection of reactive oxygen species. J Biochem Biophys Methods 65:45-80.
43. Grossbard L, Schimke RT (1966) Multiple hexokinases of rat tissues. Purification and comparison of soluble forms. J Biol Chem 241:3546-3560.
44. Guerrero Beltrán CE, Calderón Oliver M, Pedraza Chaverri J, Chirino YI (2010) Protective effect of sulforaphane against oxidative stress: recent advances. Exp Toxicol Pathol doi:10.1016/j.etp.2010.11.005
45. Herrero Mendez A, Almeida A, Fernández E, Maestre C, Moncada S, Bolaños JP (2009) The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1. Nat Cell Biol 11:747-752.
46. Hertz L (2004) The astrocyte-neuron lactate shuttle: a challenge of a challenge. J Cereb Blood Flow Metab 24:1241-1248.
47. Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219-249.
48. Hothersall JS, Baquer N, Greenbaum AL, McLean P (1979) Alternative pathways of glucose utilization in brain. Changes in the pattern of glucose utilization in brain during development and the effect of phenazine methosulfate on the integration of metabolic routes. Arch Biochem Biophys 198:478-492.
49. Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, Shulman RG (2006) Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J Cereb Blood Flow Metab 26:865-877.
50. Itoh Y, Abe T, Takaoka R, Tanahashi N (2004) Fluorometric determination of glucose utilization in neurons in vitro and in vivo. J Cereb Blood Flow Metab 24:993-1003.
51. Jolivet R, Allaman I, Pellerin L, Magistretti PJ, Weber B (2010) Comment on recent modeling studies of astrocyte-neuron metabolic interactions. J Cereb Blood Flow Metab 30:1982-1986.
52. Jomova K, Vondrakova D, Lawson M, Valko M (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345:91-104.
53. Kline CL, Schrufer TL, Jefferson LS, Kimball SR (2006) Glucosamine-induced phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 is mediated by the protein kinase R-like endoplasmic-reticulum associated kinase. Int J Biochem Cell Biol 38:1004-1014.
54. Kregel KC, Zhang HJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292:R18-R36.
55. Kruyt ND, Biessels GJ, Devries JH, Roos YB (2010) Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management. Nat Rev Neurol 6:145-155.
56. Lo MC, Lu CI, Chen MH, Chen CD, Lee HM, Kao SH (2010) Glycoxidative stress-induced mitophagy modulates mitochondrial fates. Ann NY Acad Sci 1201:1-7.
57. Macdougall NJ, Muir KW (2011) Hyperglycaemia and infarct size in animal models of middle cerebral artery occlusion: systematic review and metaanalysis. J Cereb Blood Flow Metab 31:807-818.
58. Madsen PL, Cruz NF, Sokoloff L, Dienel GA (1999) Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue. J Cereb Blood Flow Metab 19:393-400.
59. Magistretti PJ, Pellerin L, Rothman DL, Shulman RG (1999) Energy on demand. Science 283:496-497.
60. Mangia S, Simpson IA, Vannucci SJ, Carruthers A (2009) The in vivo neuronto-astrocyte lactate shuttle in human brain: evidence from modeling of measured lactate levels during visual stimulation. J Neurochem 109 (Suppl. 1):55-62.
61. Manschot SM, Biessels GJ, Valk H, Algra A, Rutten GEHM, Grond J, Kappelle LJ (2007) Metabolic and vascular determinants of impaired cognitive performance and abnormalities on brain magnetic resonance imaging in patients with type 2 diabetes. Diabetologia 50:2388-2397.
62. Matthews JA, Belof JL, Acevedo-Duncan M, Potter RL (2007) Glucosamineinduced increase in Akt phosphorylation corresponds to increased endoplasmic reticulum stress in astroglial cells. Molecular and cellular biochemistry 298:109-123.
63. McCall AL (2005) Altered glycemia and brain:update and potential relevance to the aging brain. Neurobiol Aging 26 (Suppl. 1):70-75.
64. McCormick M, Hadley D, McLean JR, Macfarlane JA, Condon B, Muir KW (2010) Randomized, controlled trial of insulin for acute poststroke hyperglycemia. Ann Neurol 67:570-578.
65. Mehta SL, Manhas N, Raghubir R (2007) Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev 54:34-66.
66. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA, J Am Med Assoc 295:1681-1687.
67. Nehlig A, Wittendorp Rechenmann E, Lam CD (2004) Selective uptake of [14C]2-deoxyglucose by neurons and astrocytes: high-resolution microautoradiographic imaging by cellular 14C-trajectography combined with immunohistochemistry. J Cereb Blood Flow Metab 24:1004-1014.
68. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787-790.
69. Orzi F, Lucignani G, Dow-Edwards D, Namba H, Nehlig A, Patlak CS, Pettigrew K, Schuier F, Sokoloff L (1988) Local cerebral glucose utilization in controlled graded levels of hyperglycemia in the conscious rat. J Cereb Blood Flow Metab 8:346-356.
70. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH, Hotamisligil GS (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306:457-461.
71. Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 91:10625-10629.
72. Pellerin L, Magistretti PJ (2003) Food for thought: challenging the dogmas. J Cereb Blood Flow Metab 23:1282-1286.
73. Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251-1262.
74. Prichard J, Rothman D, Novotny E, Petroff O, Kuwabara T, Avison M, Howseman A, Hanstock C, Shulman R (1991) Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. Proc Natl Acad Sci USA 88:5829-5831.
75. Quinn TJ, Lees KR (2009) Hyperglycaemia in acute stroke - to treat or not to treat. Cerebrovasc Dis 27(Suppl. 1):148-155.
76. Rasheva VI, Domingos PM (2009) Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis 14:996-1007.
77. Roncero I, Alvarez E, Chowen JA, Sanz C, Rábano A, Vázquez P, Blázquez E (2004) Expression of glucose transporter isoform GLUT-2 and glucokinase genes in human brain. J Neurochem 88:1203-1210.
78. Roncero I, Alvarez E, Vazquez P, Blazquez E (2000) Functional glucokinase isoforms are expressed in rat brain. J Neurochem 74:1848-1857.
79. Roncero I, Sanz C, Alvarez E, Vazquez P, Barrio PA, Blazquez E (2009) Glucokinase and glucokinase regulatory proteins are functionally coexpressed before birth in the rat brain. J Neuroendocrinol 21:973-9781.
80. Ryan CM (2006) Diabetes and brain damage: more (or less) than meets the eye? Diabetologia 49:2229-2233.
81. Sage AT, Walter LA, Shi Y, Khan MI, Kaneto H, Capretta A, Werstuck GH (2010) Hexosamine biosynthesis pathway flux promotes endoplasmic reticulum stress, lipid accumulation, and inflammatory gene expression in hepatic cells. Am J Physiol Endocrinol Metab 298:E499-E511.
82. Schernhammer E, Hansen J, Rugbjerg K, Wermuth L, Ritz B (2011) Diabetes and the risk of developing parkinson's disease in Denmark. Diabetes Care 34:1102-1108.
83. Schuier F, Orzi F, Suda S, Lucignani G, Kennedy C, Sokoloff L (1990) Influence of plasma glucose concentration on lumped constant of the deoxyglucose method: effects of hyperglycemia in the rat. J Cereb Blood Flow Metab 10:765-773.
84. Sima AAF (2010) Encephalopathies: the emerging diabetic complications. Acta Diabet 47:279-293.
85. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76-85.
86. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897-916.
87. Sommerfield AJ, Deary IJ, Frier BM (2004) Acute hyperglycemia alters mood state and impairs cognitive performance in people with type 2 diabetes. Diabetes Care 27:2335-2340.
88. Surh YJ, Kundu JK, Na HK (2008) Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 74:1526-1539.
89. Takahashi S, Driscoll BF, Law MJ, Sokoloff L (1995) Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia. Proc Natl Acad Sci USA 92:4616-4620.
90. Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, Yamamoto M, Biswal S (2002) Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res 62:5196-5203.
91. Uyttenboogaart M, Koch MW, Stewart RE, Vroomen PC, Luijckx GJ, De Keyser J (2007) Moderate hyperglycaemia is associated with favourable outcome in acute lacunar stroke. Brain 130:1626-1630.
92. Vargas MR, Johnson JA (2009) The Nrf2-ARE cytoprotective pathway in astrocytes. Expert Rev Mol Med 11:e17.
93. Vaughn AE, Deshmukh M (2008) Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c. Nat Cell Biol 10:1477-1483.
94. Wamelink MM, Struys EA, Jakobs C (2008) The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis 31:703-717.
95. Waniewski RA, Martin DL (2004) Astrocytes and synaptosomes transport and metabolize lactate and acetate differently. Neurochem Res 29:209-217.
96. Xu H, Zhou Y-l, Zhang X-Y, Lu P, Li G-S (2010) Activation of PERK signaling through fluoride-mediated endoplasmic reticulum stress in OS732 cells. Toxicology 277:1-5.
97. Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, Chen H (2011) Diabetes and risk of Parkinson's disease. Diabetes Care 34: 910-915.
98. Xu WL, von Strauss E, Qiu CX, Winblad B, Fratiglioni L (2009) Uncontrolled diabetes increases the risk of Alzheimer's disease: a population-based cohort study. Diabetologia 52:1031-1039.