Cyclosporine A-induced Decrease in Calbindin-D 28 kDa in Rat Kidney but not in Cerebral Cortex and Cerebellum

Varela, Maria del Carmen; Arce, Agustı́n; Greiner, Brigitte; Schwald, Marianne; Aicher, Lothar; Wahl, Daniel R.; Grenet, Olivier; Steiner, Sandra

doi:10.1016/s0006-2952(98)00025-2

Cited by 10 publications

(3 citation statements)

References 23 publications

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“…On the other hand, these neurons have been proposed as a heterogeneous population depending upon their expression of neurotransmitters, neuropeptides, and enzymes synthesizing neurotransmitters. Using monoclonal antibodies directed against cell-specific proteins, Purkinje cells can be categorized as Zebrin 2 (Aldolase C), P-path, Purkinje cell protein-2 [11], P400 [12, 13], and calbindin-D28K [14] subtypes. In application, CB-28 has been indicated as an excellent neuroanatomic marker for neuronal subpopulations including Purkinje cells [15, 16], while CB-28 immunoreactivity as a pathophysiological marker remains obscure.…”

Section: Introductionmentioning

confidence: 99%

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

Cui

Pierce²,

Light³

et al. 2010

CNR

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The present study aimed at identifying early damage index in the cerebellum following total body irradiation (TBI). Adult male CD2F1 mice (n=18) with or without TBI challenge (8.5 Gy irradiation) were assessed for histology and expression of selected immunohistochemical markers including malondiadehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), protein 53 (p53), vascular endothelial growth factor receptor 2 (VEGF-R2), CD45, calbindin D-28k (CB-28) and vesicular glutamate transport-2 (VGLUT2) in cerebellar folia II to IV. Compared to sham-controls, TBI significantly increased vacuolization of the molecular layer. At high magnification, deformed fiber-like structures were found along with the empty matrix space. Necrotic Purkinje cells were identified on 3.5 days after TBI, but not on 1 day. Purkinje cell count was reduced significantly 3.5 days after TBI. Compared with sham control, overall intensities of MDA and 8-OHdG immunoreactivities were increased dramatically on 1 and 3.5 days after TBI. Expression of VEGF-R2 was identified to be co-localized with 8-OHdG after TBI. This validates microvessel endothelial damage. The p53 immunoreactivities mainly deposited in the granular layer and microvessels after TBI and co-localization of the p53 with the CD45, both which were found within the microvessels. After TBI, CB28 expression decreased whereas the VGLUT2 expression increased significantly; Purkinje cells exhibited a reduced body size and deformity of dendritic arbor, delineated by CB28 immunoreactivity. Substantial damage to the cerebellum can be detectable as early as 1– 3.5 days in adult animals following sublethal TBI. Oxidative stress, inflammatory response and calcium neurotoxicity-associated mechanisms are involved in radiation-induced neuronal damage.

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Section: Introductionmentioning

confidence: 99%

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

Cui

Pierce²,

Light³

et al. 2010

CNR

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“…The liver toxicity was found to be due to the protein adducts formed by methapyrilene, specifically in mitochondrion of rat liver, which was used to model this effect. 75 In addition, the toxic effects of cyclosporine A, an immunosuppressant, in rat kidney 76 and brain 77 were also state art state art discovered with the aid of two-dimensional gel electrophoresis. Protein arrays, which are conceptually similar to high-density SNP and gene expression measurements, are just emerging as potent tools to aid new studies in drug toxicity.…”

Section: Newer Types Of Molecular Measurementsmentioning

confidence: 99%

Data-Driven Methods to Discover Molecular Determinants of Serious Adverse Drug Events

Chiang

Butte

2009

Clin Pharmacol Ther

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The dangers of serious ADR (SADR) are well known by clinicians, pharmacologists, and the lay public. The ascertainment of the molecular mechanisms behind SADRs has made significant progress through genetics and gene expression measurements. But as the field of pharmacology adopts the same novel higher-density measurement modalities that have proven successful in other areas of biology, one wonders whether there can be more ways to benefit from the explosion of data created by these tools. The development of analytic tools and algorithms to interpret these biological data to create tools for medicine is central to the field of translational bioinformatics. After we introduce some of the types of SADR predictors we need, we will cover several publicly-available databases available for the study of SADRs, scaling from clinical to molecular measurements. We will then demonstrate recent examples of how bioinformatics methods coupled with data repositories can advance the science of SADRs.

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“…Other examples of studies in which 2DE has been used in drug development include the characterization of Cyclosporin A toxicity in rat kidney 21 and brain, 22 and the proteinlevel characterization of histopathologies observed in the liver during preclinical assessment of drug candidates (substituted pyrimidine derivatives). 23 The hepatic effects of cholesterol-lowering statin drugs (HMG-CoA reductase inhibitors) such as lovastatin (eg, Mevacor s , a natural product) and fluvastatin (eg, Lescol s , a totally synthetic product), also have been investigated.…”

Section: Two-dimensional Gel Electrophoresis (2de) and Mass Spectromementioning

confidence: 99%

Pharmacoproteomics in drug development

Witzmann

Grant

2003

Pharmacogenomics J

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The field of proteomics is taking on increased significance as the relevance of investigating and understanding protein expression in disease and drug development is appreciated. Recent advances in proteomics have been driven by the availability of numerous annotated whole-genome sequences and a broad range of technological and bioinformatic developments that underscore the complexity of the proteome. This review briefly addresses some of the various technologies that comprise Expression Proteomics and Functional Proteomics, citing examples where these emerging approaches have been applied to pharmacology, toxicology, and the development of drugs.

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Cyclosporine A-induced Decrease in Calbindin-D 28 kDa in Rat Kidney but not in Cerebral Cortex and Cerebellum

Cited by 10 publications

References 23 publications

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

Data-Driven Methods to Discover Molecular Determinants of Serious Adverse Drug Events

Pharmacoproteomics in drug development

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