Significant change in insulin production, glucose tolerance and ER stress signaling in transgenic mice coexpressing insulin-siRNA and human IDE

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Abstract. Selenoprotein is associated with a variety of serious diseases, including infectious diseases, neurodegenerative disorders, cancer and cardiovascular disease. The aim of this study was to produce a new transgenic (Tg) rat expressing human selenoprotein M (SelM) in order to examine the protective function of the antioxidant status in vivo. To achieve this, a new lineage of Tg rats was produced by the microinjection of pCMV/GFP-hSelM constructs into a fertilized rat egg. Several conclusions can be drawn based on the results of the present study. The human SelM gene was successfully expressed at both the transcription and protein levels in the CMV/GFP-hSelM Tg rats. This Tg rat showed a different enzyme activity for the antioxidant protein in the various tissues examined. In response to the 2,2'-azobiz(2-amidinopropane) dihydrochloride (AAPH) injection, the Tg rats showed a lower level of antioxidant and H 2 O 2 concentration as the activity of the antioxidant enzyme was maintained at a higher level in the Tg rats than in the non-Tg rats. Also, the neutrophil-to-lymphocyte ratio was significantly increased in this Tg rat, even though the level of corticosterone remained unchanged in both genotypes. Thus, the results of this study demonstrated that the CMV/GFP-hSelM Tg rat can serve as an animal model for the maintenance of a high level of antioxidant status and can be used to study the biological function of selenoprotein in infectious diseases, cardiovascular disease and cancer.

“…Immunohistochemical analysis was performed as previously described (11,12). Briefly, the level Figure 1.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Hwang¹,

Sin²,

Kim³

et al. 2008

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“…the pCMV/ hGATA3 plasmid was digested with Bglii/Pvuii in order to remove the prokaryotic sequence, and then microinjected into the male pronucleus of fertilized embryos, which had been obtained by crossing c57Bl/6 (female) mice with dBa/2 (male) mice. the injected egg was then transferred into the oviducts of a pseudopregnant icr recipient female (15). the transgene was identified by Pcr analysis of the genomic dna isolated from the tails of the 3-week-old founder mice.…”

Section: Methodsmentioning

confidence: 99%

GATA binding protein 3 overexpression and suppression significantly contribute to the regulation of allergic skin inflammation

Bae

Lee²,

Shim³

et al. 2011

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Abstract. Gata binding protein 3 (Gata3) is a key molecule regulating the balance in the ratio of type 1 helper t (th1) cells to type 2 helper t (th2) cells, which is thought to be indicative of the pathogenesis of allergic diseases such as asthma and atopic dermatitis. the aim of this study was to investigate the role of GATA3 in allergic skin inflammation. transgenic (tg) mice overexpressing human Gata3 (hGata3) were produced by the microinjection of pCMV/hGATA3 constructs into fertilized mouse eggs. the hGata3 gene was successfully expressed at the protein level in the lymph node and thymus of cmV/hGata3 transfected cells and tg mice. CMV/hGATA3 Tg mice showed a significant increase in the allergic skin inflammation response such as ear thickness, draining auricular lymph node (aln) weight, epidermal thickness, inflammatory cell number and Th2 immunoglobulin (Ig) concentration compared to wild-type (Wt) mice after phthalic anhydride (Pa) treatment. furthermore, the secretion of th2 type cytokines was increased by Pa treatment in cmV/ hGata3 tg mice, while the secretion of th1 type cytokine was suppressed under the same conditions. However, the increased levels of th2 type cytokines in cmV/hGata3 tg mice were almost recovered by the down-regulation of Gata3 expression with D-pinitol treatment. Therefore, these findings suggest that Gata3 could be considered as a potential target regulating the mechanism responsible for the differences in allergic skin inflammation. Introductionallergic diseases, such as asthma, rhinitis and atopic dermatitis, are characterized by inflammation driven by type 2 helper T (th2) cells (1). in allergic individuals, the exposure to allergens results in activation of antigen-specific type 2 helper (Th2) cells and secretion of a variety of cytokines and inflammatory mediators that provoke the inflammatory response (2).th2 cytokines are predominantly regulated by the Gata binding protein 3 (Gata3). the zinc-finger transcription factor Gata3 is the master regulator of th2 cell differentiation and is strongly up-regulated during th2 differentiation (3). Generally, th1 and th2 cells are differentiated from common t precursor cells in the t cell developmental process (4,5). Two polarized subsets can be identified on the basis of the class of cytokines which secreted from each cell. th1 cells mainly secrete il-2 and ifn-γ, while th2 cells secrete il-4, il-5, il-6, il-10 and il-13 (6). Gata3 is believed to function by causing chromatin remodeling of the th2 cytokine locus by binding at multiple promoter sites and thus allowing th2 cells to express il-4, il-5 and il-13 (7,8). furthermore, several studies using Gata-3 deletion mutants have suggested that the Gata3 protein plays an important role in vertebrate development and th2 differentiation (9,10). in addition, transgenic (tg) mice that overexpress Gata3 spontaneously have asthma-like symptoms. in these mice, the number of Gata3-positive cells is increased in the asthmatic lung and in allergic rhinitis, while these cells are found to furthe...

“…In addition, β-cell apoptosis is considered as one of the main reasons of β-cell dysfunction (1,8). Endoplasmic reticulum (ER) stress has been suggested as a causing factor of β-cell dysfunction and apoptosis (2)(3)(4)(5)(6). However, the underlying mechanisms remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic β-cell apoptosis

Peng

Men²,

Zhang³

et al. 2011

Abstract. Pancreatic β-cell dysfunction is a critical component in the pathogenesis of diabetes. Endoplasmic reticulum (ER) stress is one of the factors that induces pancreatic β-cell dysfunction, but the underlying mechanisms have not been well elucidated. In this study, we report that a mitochondrial fission modulator, dynamin-related protein 1 (DRP-1), plays an important role in ER stress-induced β-cell apoptosis. Induction of dRP-1 expression significantly promoted ER stress-induced apoptosis in the dRP-1 WT (dRP-1 wildtype) inducible β-cell line, but not in the dRP-1 K38A (a dominant negative mutant of dRP-1) inducible β-cell line. We further demonstrated that the mitochondrial membrane potential decreased, and that cytochrome c release, caspase-3 activation and generation of reactive oxygen species (ROS) were enhanced by induction of dRP-1 WT, but prevented by dRP-1 K38A in pancreatic β-cells under ER stress conditions. These results indicate that dRP-1 mediates ER stress-induced pancreatic β-cell apoptosis.