Disease relevance of Bovinocidin

• Because in vivo trauma models and clinical head injury have associated cerebral ischemia and/or metabolic impairment, we transiently impaired cellular metabolism after mechanical trauma of neuronal-glial cultures by combining 3-nitropropionic acid treatment with concurrent glucose deprivation [1].
• We have investigated whether in vivo toxicity of the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP) can be attenuated by constitutive and inducible Nrf2 activity [2].
• In transgenic mice 3-nitropropionic acid induced or augmented motor deficits that were associated with MSA-like pathology including striatonigral degeneration and olivopontocerebellar atrophy [3].
• Pretreatment with ASA in vitro or in vivo decreased the decline of ATP content during hypoxic hypoxia and chemical hypoxia (inhibition of succinic dehydrogenase by 3-nitropropionic acid) [4].
• Many studies have reported ischemia protection using various preconditioning techniques, including single dose 3-nitropropionic acid (3-NPA), a mitochondrial toxin [5].

Psychiatry related information on Bovinocidin

• Magnetic resonance imaging and spectroscopy in assessing 3-nitropropionic acid-induced brain lesions: an animal model of Huntington's disease [6].
• Locomotor activity in rats infused with 3-nitropropionic acid (15 mg/kg/day, for four weeks) via subcutaneous osmotic minipumps was considerably reduced compared to control rats [7].
• During spatial discrimination learning (invisible platform) in the Morris Water Maze task the swimming velocity was decreased in both rat strains as a result of 3-nitropropionic acid treatment [8].

High impact information on Bovinocidin

• We have previously reported that treatment with tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, prevented neuropathology and associated behavioral deficits in the 3-nitropropionic acid rat model of HD [9].
• Moreover, mutant cells exhibited mitochondrial respiratory chain impairment, evidenced by decreased ATP and ATP/ADP ratio, impaired MTT conversion and heightened sensitivity to 3-nitropropionic acid [10].
• To test this mitochondrial hypothesis, we studied the effects in rodents and non-human primates of a chronic blockade of succinate oxidation by systemic administration of the mitochondrial toxin 3-nitropropionic acid (3NP) [11].
• Inhibitors of mitochondrial oxidative phosphorylation (rotenone or 3-nitropropionic acid) or of glycolysis (iodoacetate plus pyruvate) also produced only partial ATP depletion, suggesting that either process alone could partially maintain ATP stores [12].
• Ablation of the subthalamic nucleus supports the survival of nigral dopaminergic neurons after nigrostriatal lesions induced by the mitochondrial toxin 3-nitropropionic acid [13].

Chemical compound and disease context of Bovinocidin

• Dopamine modulates the susceptibility of striatal neurons to 3-nitropropionic acid in the rat model of Huntington's disease [14].
• An impaired complex II (succinate dehydrogenase, SD) striatal mitochondrial activity is one of the prominent metabolic alterations in Huntington's disease (HD), and intoxication with 3-nitropropionic acid (3-NP), an inhibitor of mitochondrial complex II, mimics the motor abnormalities and the pathology of HD [15].
• 3-Nitropropionic acid toxicity in hippocampus: Protection through N-methyl-D-aspartate receptor antagonism [16].
• Creatine exhibited significant neuroprotection against toxicity instigated either by glucose- and serum deprivation or addition of 3-nitropropionic acid [17].
• Overexpression of GT from these vectors protected cultured hippocampal, spinal cord, and septal neurons against various necrotic insults, including hypoglycemia, glutamate, and 3-nitropropionic acid [18].

Biological context of Bovinocidin

• To determine the role of compromised mitochondrial function in the neuronal cell death in HD, immortalized striatal cells established from Hdh(Q7) (wild-type) and Hdh(Q111) (mutant) mouse knock-in embryos were treated with 3-nitropropionic acid (3-NP), a mitochondrial complex II toxin [19].
• Mechanisms of cell death induced by the mitochondrial toxin 3-nitropropionic acid: acute excitotoxic necrosis and delayed apoptosis [20].
• Oxidative stress and excitotoxicity have been implicated in selective striatal vulnerability caused by the mitochondrial toxin, 3-nitropropionic acid (3-NP), which may simulate Huntington's disease in animals and humans [21].
• Involvement of superoxide in excitotoxicity and DNA fragmentation in striatal vulnerability in mice after treatment with the mitochondrial toxin, 3-nitropropionic acid [21].
• The mitochondrial toxin 3-nitropropionic acid (3-NP) has been largely used to study neurodegenerative disorders in which bioenergetic defects are implicated [22].

Anatomical context of Bovinocidin

• PC12 cell lines expressing a PS-1 mutation (L286V) exhibited increased sensitivity to apoptosis induced by 3-nitropropionic acid (3-NP) and malonate, inhibitors of succinate dehydrogenase, compared with control cell lines and lines overexpressing wild-type PS-1 [23].
• The effect of melatonin (1 mg/kg BW i.p./day) on the oxidative changes produced by 3-nitropropionic acid (20 mg/kg BW/day for 4 days) in rat striatal and cortical synaptosomes was investigated [24].
• 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of complex II in the mitochondria [25].
• We have investigated the effectiveness of transplantation of human neural stem cells into adult rat striatum prior to induction of striatal damage with the mitochondrial toxin 3-nitropropionic acid (3-NP) [26].
• Continuous systemic administration of low doses of 3-nitropropionic acid for 1 month resulted in striatal lesions showing growth-related changes in dendrites of striatal spiny neurons using the Golgi technique [27].

Associations of Bovinocidin with other chemical compounds

• Mitochondrial toxins like 3-nitropropionic acid (3-NP) and malonate, functioning as the inhibitors of the complex II of mitochondrial respiratory chain, have been found to effectively induce specific behavioral changes and selective striatal lesions in rats and non-human primates mimicking those in HD [6].
• We tested whether mice that are deficient in dihydrolipoamide dehydrogenase (Dld+/-) show increased vulnerability to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), malonate and 3-nitropropionic acid (3-NP), which have been proposed for use in models of PD and HD [28].
• Exposure of synaptosomes to oxidative insults (amyloid beta-peptide and Fe(2+)) and a metabolic insult (the mitochondrial toxin 3-nitropropionic acid) resulted in decreased levels of glucose uptake [29].
• A novel enzyme that catalyses the oxygen-dependent oxidation of 3-nitropropionic acid (3NPA) to malonate semialdehyde, nitrate, nitrite and H2O2 has been purified from leaf extracts of the horseshoe vetch, Hippocrepis comosa, and named 3NPA oxidase [30].
• Similarly, celastrol significantly decreased the striatal lesion volume induced by 3-nitropropionic acid, a neurotoxin used to model HD in rats [31].

Gene context of Bovinocidin

• Previously, uridine pro-drug 2',3',5'-tri-O-acetyluridine (PN401) was shown to be protective in the mitochondrial complex II inhibitor 3-nitropropionic acid model of Huntington's disease (HD) [32].
• Cultured human astrocytes exposed to 3-nitropropionic acid, an established model of neuronal hypoxia, increased VEGF expression, as expected, but also increased expression of crystallins [33].
• The effect of aging on p38 signaling pathway activity in the mouse liver and in response to ROS generated by 3-nitropropionic acid [34].
• Malonate and 3-nitropropionic acid neurotoxicity are reduced in transgenic mice expressing a caspase-1 dominant-negative mutant [35].
• Death of striatal neurons induced by 3-nitropropionic acid was markedly reduced after induced TGF-beta1 expression [36].

Analytical, diagnostic and therapeutic context of Bovinocidin

• 3-Nitropropionic acid-induced neurotoxicity--assessed by ultra high resolution positron emission tomography with comparison to magnetic resonance spectroscopy [37].
• In addition, we noted that astrocytic cell death occurred in 9% of cells at 60 min or more after the start of a 40 min perfusion with 3-nitropropionic acid, while only 4% of neurons died [38].
• In a protocol of intraperitoneal injection, toxicity of 3-nitropropionic acid was highest in Fisher rats, intermediate in Sprague-Dawley rats and lowest in Lewis rats [39].
• These results revealed that sex ovarian hormones play a important role in onset and development of neurodegenerative diseases, as well as neuroprotective effects of 17 beta-estradiol against the changes induced ovariectomy and ovariectomy plus 3-nitropropionic acid [40].
• The effect of 3-nitropropionic acid (3-NPA) on intracellular calcium ([Ca2+]i) in cultured cortical and striatal astrocytes was examined using a calcium imaging technique with fura-2 [41].

References