Evidence of Oxidative Stress in the Brains of Fetuses with CNS Anomalies and Islet Cell Hyperplasia

Hockett, Patricia K.; Emery, Shawn Clark; Hansen, Lawrence A.; Masliah, Eliezer

doi:10.1007/s10024-001-0130-2

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…Non-glucose treated astrocytes transduced with Nef virus also showed an increase in total nitrate, however, the level of production was relatively lower than that observed in astrocytes with hyperglycemia. These results are fully consistent with the results of other studies, which have shown that hyperglycemic conditions may contribute to CNS malformation via oxidative stress[33,47]. …”

Section: Discussionsupporting

confidence: 93%

Combined effects of hyperglycemic conditions and HIV-1 Nef: a potential model for induced HIV neuropathogenesis

Acheampong¹,

Roschel

Mukhtar

et al. 2009

Virol J

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Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and the production of total nitrate and 8-iso-PGF2 α as reactive oxygen species (ROS) in human astrocytes leading to cell death in a dose-dependent manner. Delivery of purified recombinant HIV-1 Nef protein, or Nef expressed via HIV-1-based vectors in astrocytes showed similar results. The expression of Nef protein delivered via HIV-1 vectors in combination with hyperglycemia further augmented the production of ROS, C3, activation of caspase-3, modulation of filamentous protein (F-protein), depolarization of the mitochondria, and loss of astrocytes. To further verify the effects of hyperglycemia and HIV-1 Nef protein on CNS individually or in combination, in vivo studies were performed in streptozotocin (STZ) induced diabetic mice, by injecting HIV-1 Nef expressing viral particles into the sub-cortical region of the brain. Our in vivo results were similar to in vitro findings indicating an enhanced production of caspases-3, ROS (lipid oxidation and total nitrate), and C3 in the brain tissues of these animals. Interestingly, the delivery of HIV-1 Nef protein alone caused similar damage to CNS as augmented by hyperglycemia conditions. Taken together, the data suggests that HIV-1 infected individuals with hyperglycemia could potentially be at a higher risk of developing CNS related complications.

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Section: Discussionsupporting

confidence: 93%

Combined effects of hyperglycemic conditions and HIV-1 Nef: a potential model for induced HIV neuropathogenesis

Acheampong¹,

Roschel

Mukhtar

et al. 2009

Virol J

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“…As already discussed, in the presence of ROS, NO can lead to the formation of peroxynitrite, a reaction that limits NO bioactivity and causes severe tissue damage [21]. Increased peroxynitrite-induced nitrotyrosylation has been detected in brains of human demised fetuses when islet cell hyperplasia indicates fetal hyperglycemia [155]. Also, increased nitrotyrosine has been found in human umbilical endothelial cells cultured under hyperglycemic conditions, through mechanisms that seem to involve the peroxynitrite-induced activation of poly-ADP ribose polymerase [23].…”

Section: Maternal Diabetes-induced Pro-inflam-matory Mediators In Thementioning

confidence: 97%

Diabetic Pregnancies: The Challenge of Developing in a Pro-Inflammatory Environment

Jawerbaum

González²

2006

CMC

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The maternal diabetic environment alters the embryo and the feto-placental development. The results of these alterations are: increased embryo resorption and malformation rates, placental dysfunction, fetal alterations that lead to increased neonatal morbidity and mortality rates, and also diseases that will be evident later in the adult life of the newborn. The etiology of these many maternal diabetes-induced complications are not yet understood in full. In this review the role of maternal diabetes as an inductor of a pro-inflammatory environment that impairs embryo and placental development is discussed. An overproduction of pro-inflammatory agents is found in the uterus during implantation and the developing embryo and placenta from experimental models of diabetes, as well as in placenta from diabetic women. In these tissues there are increases in reactive oxygen species, pro-inflammatory cytokines and prostaglandins, nitric oxide and peroxynitrites. These pro-inflammatory agents lead to the intrauterine activation of matrix metalloproteinases, proteases involved in remodeling the extracellular matrix during implantation and feto-placental development. Many of these pro-inflammatory agents have overlapping mechanisms of action and cross regulatory pathways that propagate the inflammatory processes. Antioxidants, PPARgamma activators, and NF-kappaB inhibitors are able to reduce the concentrations of these agents in intrauterine gestational tissues. This article reviews the current understanding of maternal diabetes-induced changes in pro-inflammatory and anti-inflammatory pathways that affect the embryo and placental development in maternal diabetes, and stresses the need of a strict maternal control of the pathology to prevent deleterious consequences in the offspring.

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“…An increased nitrotyrosine expression in CA1 pyramidal neurons has been previously demonstrated in foetuses exposed to hyperglycemia because of maternal diabetes (Hockett et al, 2004), but our work provides the first evidence of enhanced hippocampal nitrotyrosine in an adult model of experimental diabetes and identifies the CA1 pyramidal neuron layer as a specific site of enhanced peroxynitrite formation. Of interest a recent study has shown a strong nitrotyrosine immunoreactivity of CA1 pyramidal neurons in mice expressing a mutated form of SOD (Cha et al, 2000), providing evidence of a causal link between oxidative stress and nitrotyrosine expression in this region.…”

Section: Discussionmentioning

confidence: 75%

Hippocampal heat shock protein 25 expression in streptozotocin-induced diabetic mice

Mastrocola¹,

Barutta²,

Pinach³

et al. 2012

Neuroscience

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Hippocampal abnormalities are believed to increase the risk of cognitive decline in diabetic patients. The underlying mechanism is unknown, but both hyperglycemia and oxidative stress have been implicated. Cellular stresses induce expression of heat shock protein 25 (HSP25) and this results in cytoprotection. Our aim was to assess hippocampal expression of HSP25 in experimental diabetes. Mice were rendered diabetic by streptozotocin injection. Ten weeks after diabetes onset hippocampal HSP25 expression was studied by immunoblotting and immunohistochemistry (IHC).Expression of glial fibrillary acidic protein (GFAP), nitrotyrosine, iNOS, HSP72, HSP90, and Cu/Zn superoxide dismutase (SOD) was assessed by either IHC or immunoblotting, Cu/Zn-SOD activity by enzymatic assay, and malondialdehyde (MDA) content by colorimetric assay.Hippocampal HSP25 was significantly increased in diabetic as compared to non-diabetic animals and localised predominantly within the pyramidal neurons layer of the CA1 area. This was paralleled by overexpression of nitrotyrosine, iNOS, SOD expression/activity, and enhanced MDA content. In experimental diabetes, HSP25 is overexpressed in the CA1 pyramidal neurons in parallel

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Evidence of Oxidative Stress in the Brains of Fetuses with CNS Anomalies and Islet Cell Hyperplasia

Cited by 10 publications

References 34 publications

Combined effects of hyperglycemic conditions and HIV-1 Nef: a potential model for induced HIV neuropathogenesis

Combined effects of hyperglycemic conditions and HIV-1 Nef: a potential model for induced HIV neuropathogenesis

Diabetic Pregnancies: The Challenge of Developing in a Pro-Inflammatory Environment

Hippocampal heat shock protein 25 expression in streptozotocin-induced diabetic mice

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