SUMO2/3 is Associated with Ubiquitinated Protein Aggregates in the Mouse Neocortex after Middle Cerebral Artery Occlusion

Hochrainer, Karin; Jackman, Katherine; Benakis, Corinne; Anrather, Josef; Iadecola, Costantino

doi:10.1038/jcbfm.2014.180

Cited by 46 publications

(66 citation statements)

References 15 publications

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“…Relatively few previous efforts to make a T1 agent for this application have been made [4,6,15], and to our knowledge, none have yet been successful in imaging plaques in vivo following intravenous injection. Kim et al demonstrated [10,11,16] a hollow manganese oxide nanoparticle targeted using the amyloid peptide as a targeting ligand. It was delivered by intracranial injection into the cisterna magna and did not have to negotiate the blood-brain barrier.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic Resonance Imaging

Tanifum

Ghaghada

Vollert

et al. 2016

JAD

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Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid deposits in dog brain and human brain tissue ex vivo. The ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. The preparation was tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates and Indocyanine green were included in the particles for visualization by MRI and near-infrared microscopy. Upon intravenous injection, the particles successfully traversed the blood-brain barrier in these mice, and bound to the plaques. Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated elevated signal in the brains of mice with amyloid plaques present. No signal was observed in amyloid-negative mice, or in amyloid-positive mice injected with an untargeted version of the same agent. The MRI results were confirmed by immunohistochemical and fluorescent microscopic examination of mouse brain sections, showing colocalization of the fluorescent tags and amyloid deposits.

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Section: Introductionmentioning

confidence: 99%

“…To determine how these particles were successful in penetrating the BBB, we conducted [15,16] a subsequent study of BBB permeation of untargeted liposomes in the TetO/APP mouse model of AD. This model features the Swedish and Indiana mutations of the APP gene, under the control of a tetracycline responsive element.…”

Section: Introductionmentioning

confidence: 99%

A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic Resonance Imaging

Tanifum

Ghaghada

Vollert

et al. 2016

JAD

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“…Between the heart and the surface vessels of the brain from which we measured flow and volume signals (Blinder et al, 2010; 2013; Chen et al, 2011) are the large arteries in the circle of Willis (Vrselja et al, 2014), and the initial segments of the large cerebral arteries. These large vessels at the base of the brain contribute a substantial amount to the resistance of the cerebral vascular network (Faraci and Heistad, 1990), allowing them to exert a strong regulatory influence on pressures experienced by downstream vessels in the dorsal cortex.…”

Section: Discussionmentioning

confidence: 99%

Venous cerebral blood volume increase during voluntary locomotion reflects cardiovascular changes

Huo¹,

Greene²,

Drew

2015

NeuroImage

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Understanding how changes in the cardiovascular system contribute to cerebral blood flow (CBF) and volume (CBV) increases is critical for interpreting hemodynamic signals. Here we investigated how systemic cardiovascular changes affect the cortical hemodynamic response during voluntary locomotion. In the mouse, voluntary locomotion drives an increase in cortical CBF and arterial CBV that is localized to the forelimb/hindlimb representation in the somatosensory cortex, as well as a diffuse venous CBV increase. To determine if the heart rate increases that accompany locomotion contribute to locomotion-induced CBV and CBF increases, we occluded heart rate increases with the muscarinic cholinergic receptor antagonist glycopyrrolate, and reduced heart rate with the β1-adrenergic receptor antagonist atenolol. We quantified the effects of these cardiovascular manipulations on CBV and CBF dynamics by comparing the hemodynamic response functions (HRF) to locomotion across these conditions. Neither the CBF HRF nor the arterial component of the CBV HRF was significantly affected by pharmacological disruption of the heart rate. In contrast, the amplitude and spatial extent of the venous component of the CBV HRF was decreased by atenolol. These results suggest that the increase in venous CBV during locomotion was partially driven by peripheral cardiovascular changes, whereas CBF and arterial CBV increases associated with locomotion reflect central processes.

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“…The results Recent study demonstrated that overproduction of damaged proteins following focal cerebral ischemia increases protein ubiquitination, resulting in ubiquitinated proteins aggregation. 36) Brain ischemia also damages protein degradation pathways, causing the accumulation of ubiquitinated proteins. 37) In this study, we also discovered that Z-ligustilide reduced the accumulation of ubiquitinated proteins induced by both MG132 and OGD-Reoxy and provided the evidence that blocking protein aggregation may be an important mechanism for the protection of Z-ligustilide against OGD-Reoxy induced injury.…”

Section: Discussionmentioning

confidence: 99%

Protective HSP70 Induction by Z-Ligustilide against Oxygen–Glucose Deprivation Injury <i>via</i> Activation of the MAPK Pathway but Not of HSF1

Jiang

Ning

et al. 2015

Biological & Pharmaceutical Bulletin

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Key words Z-ligustilide; heat-shock protein 70; mitogen-activated protein kinase; oxygen-glucose deprivation-reoxygenation; heat-shock factor 1The World Health Organization (WHO) Global Infobase reports that stroke has become the second leading cause of mortality in the world, causing around 6000000 deaths annually. 1)However, there are currently relatively few treatment options available to minimize damage or death following a stroke. Protein aggregates containing ubiquitinated proteins are commonly present in neurodegenerative disorders and have been considered to cause neuronal degeneration. The previous study also showed that transient cerebral ischemia caused severe protein aggregation in hippocampal CA1 neurons which appeared at 4 h and progressively accumulated at 24 and 48 h. 2)Therefore, control of protein aggregation may represent an alternative treatment to neurological damage caused by ischemic stroke.Heat shock proteins (HSPs) are a group of phylogenetically and ubiquitous cytoprotective proteins found in all prokaryotic and eukaryotic cells, many of which are chaperone molecules that facilitate protein folding, trafficking and also prevent their aggregation and degradation.3) Heat shock protein 70 (HSP70) is a major inducible heat shock protein that basically functions as a molecular chaperone and plays an important role in preventing protein aggregation, degrading unstable and misfolded proteins and transporting proteins between cellular compartments.4) It's reported that over-expression of HSP70 via transgenes and viruses or systemic administration of HSP70 fusion proteins that allow it to cross the blood brain barrier protects the brain against ischemia, 5,6) suggesting that increasing HSP70 level or activity may be a potential therapeutic target for pharmacological intervention of ischemic diseases.Ligusticum chuanxiong is a commonly used Chinese herbal medicine with its empiric treatment of cardiovascular and cerebrovascular diseases.7) Z-Ligustilide as the major bioactive phthalide compound of Rhizoma chuanxiong was previously suggested for the prevention and treatment of ischemic stroke. 8,9) Our and others' studies showed that Z-ligustilide could protect ischemic injury both in vitro and in vivo via the induction of direct and indirect antioxidant response. 8,10,11) However, its effect on the heat shock response, a highly conserved and fundamental cytoprotective mechanism, under ischemic stress remains unexplored. Along this line, we characterized the effect of Z-ligustilide on HSP70 and explored the potential role of HSP70 in the protection of Z-ligustilide against oxygen-glucose deprivation and reoxygenation (OGDReoxy) induced injury in this study.

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SUMO2/3 is Associated with Ubiquitinated Protein Aggregates in the Mouse Neocortex after Middle Cerebral Artery Occlusion

Cited by 46 publications

References 15 publications

A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic Resonance Imaging

A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic Resonance Imaging

Venous cerebral blood volume increase during voluntary locomotion reflects cardiovascular changes

Protective HSP70 Induction by Z-Ligustilide against Oxygen–Glucose Deprivation Injury <i>via</i> Activation of the MAPK Pathway but Not of HSF1

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