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Ause mitochondrial dysfunction [16], ATP deficiency [25] and apoptosis. The structural similarities between STZ and nitrosamines, including N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) [26], together with experimental evidence that high doses of STZ cause cancer while lower doses cause diabetes or AD-type neurodegeneration with cognitive impairment [15,16,22] led us to hypothesiz
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Elated compound, causes neurodegeneration, whereas peripheral treatment causes DM. Hypothesis: Limited early exposures to nitrosamines that are widely present in the environment, enhance the deleterious effects of high fat intake in promoting T2DM and neurodegeneration. Methods: Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. injection, and upon weaning, they were fed wi
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Antibody (1:10000) and Amplex Red soluble fluorophore [79]. Amplex Red fluorescence was measured (Ex 579/Em 595) in a SpectraMax M5 microplate reader (Molecular Devices Corp., Sunnyvale, CA). Negative control reactions included substitutions with nonrelevant primary or secondary antibodies, and omission of primary or secondary antibody. Immunoreactivities were normalized to protein content as dete
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In HeLa cells. Autophagy. 2011;7(1):27?9. 64. Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS. The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell. 2002;111(1):29?0. 65. Fung C, Lock R, Gao S, Salas E, Debnath J. Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol Biol
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Urs), rats were sacrificed by i.p. injection of pentobarbital (120 mg/kg). Blood and cerebella were harvested immediately. Blood or serum was used to measure glucose, insulin, cholesterol, triglycerides, and free fatty acid levels, as previously described [45,46]. Cerebella were harvested for histopathological, biochemical, and molecular studies. For histopathology, tissue samples were immersion f
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Lyclonal and monoclonal antibodies and immunodetection reagents were purchased from Abcam (Cambridge, MA), Vector Laboratories (Burlingame, CA), Upstate (Billerica, MA), Chemicon (Temecula, CA), or Molecular Probes (Eugene, OR). The insulin ultra-sensitive ELISA kit was obtained from ALPCO Diagnostics (Salem, NH). Histochoice fixative was purchased from Amresco, Inc (Solon, OH). Antibodies to tumo
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S described elsewhere [79]. For molecular and biochemical assays, cerebella were snap-frozen in a dry ice-methanol bath and stored at -80 . We studied cerebellar tissue because the cerebellum: 1) requires intact insulin/IGF signaling to maintain its structural and functional integrity [80,81]; 2) is severely damaged by i.c.-STZ mediated neurodegeneration [19,22]; 3) although relatively spared, it
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Ither the leaded or unleaded group as compared with the control. On the contrary, dopamine was elevated in the cerebellum of leaded exposed group above both the unleaded gasoline and control. The fluctuations in the levels of dopamine in different brain areas may be related to the effects MMT which is an organic manganese (Mn) compound added to unleaded gasoline and the mechanisms of Mn neurotoxic