Lack of the Histone Deacetylase SIRT1 Leads to Protection against Endoplasmic Reticulum Stress through the Upregulation of Heat Shock Proteins.

Histone deacetylase SIRT1 represses gene expression through the deacetylation of histones and transcription factors and is involved in the protective cell response to stress and aging. However, upon endoplasmic reticulum (ER) stress, SIRT1 impairs the IRE1α branch of the unfolded protein response (UPR) through the inhibition of the transcriptional activity of XBP-1 and SIRT1 deficiency is beneficial under these conditions. We hypothesized that SIRT1 deficiency may unlock the blockade of transcription factors unrelated to the UPR promoting the synthesis of chaperones and improving the stability of immature proteins or triggering the clearance of unfolded proteins.

Silent information regulator 1 protects the liver against ischemia-reperfusion injury: implications in steatotic liver ischemic preconditioning.

Ischemia-reperfusion (IR) injury is an important problem in liver surgery especially when steatosis is present. Ischemic preconditioning (PC) is the only surgical strategy that has been applied in patients with steatotic livers undergoing warm ischemia. Silent information regulator 1 (SIRT1) is a histone deacetylase that regulates various cellular processes.

Quantitative imaging of microtubule alteration as an early marker of axonal degeneration after ischemia in neurons.

Neuronal death can be preceded by progressive dysfunction of axons. Several pathological conditions such as ischemia can disrupt the neuronal cytoskeleton. Microtubules are basic structural components of the neuronal cytoskeleton that regulate axonal transport and neuronal function.

RGD-based cell ligands for cell-targeted drug delivery act as potent trophic factors.

Unlabelled: Integrin-binding, Arg-Gly-Asp (RGD)-containing peptides are the most widely used agents to deliver drugs, nanoparticles, and imaging agents. Although in nature, several protein-mediated signal transduction events depend on RGD motifs, the potential of RGD-empowered materials in triggering undesired cell-signaling cascades has been neglected. Using an RGD-functionalized protein nanoparticle, we show here that the RGD motif acts as a powerful trophic factor, supporting extracellular signal-regulated kinase 1/2 (ERK1/2)-linked cell proliferation and partial differentiation of PC12 cells, a neuronlike model.

A complementary diffusion tensor imaging (DTI)-histological study in a model of Huntington's disease.

In vivo diffusion tensor imaging (DTI) was performed on the quinolinic acid (QUIN) rat model of Huntington's disease, together with behavioral assessment of motor deficits and histopathological characterization. DTI and histology revealed the presence of a cortical lesion in 53% of the QUIN animals (QUIN(+ctx)). Histologically, QUIN(+ctx) were distinguished from QUIN(-ctx) animals by increased astroglial reaction within a subregion of the caudate putamen and loss of white matter in the external capsula.

Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism.

Purpose: Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [18F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB1) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D2 receptor availability and amphetamine-induced turning behaviour.

Methods: Twenty-one Wistar rats (11 QA and 10 shams) were investigated.

In vitro and in vivo activation of astrocytes by amyloid-beta is potentiated by pro-oxidant agents.

Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease. Age is the main risk factor for sporadic AD, which is the most prevalent type. Amyloid-beta peptide (Abeta) neurotoxicity is the proposed first step in a cascade of deleterious events leading to AD pathology and dementia.

Identification of pro-angiogenic markers in blood vessels from stroked-affected brain tissue using laser-capture microdissection.

Background: Angiogenesis correlates with patient survival following acute ischaemic stroke, and survival of neurons is greatest in tissue undergoing angiogenesis. Angiogenesis is critical for the development of new microvessels and leads to re-formation of collateral circulation, reperfusion, enhanced neuronal survival and improved recovery.

Results: Here, we have isolated active (CD105/Flt-1 positive) and inactive (CD105/Flt-1 minus (n=5) micro-vessel rich-regions from stroke-affected and contralateral tissue of patients using laser-capture micro-dissection.

Modified C-reactive protein is expressed by stroke neovessels and is a potent activator of angiogenesis in vitro.

Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue-binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri-infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons.

Spermine induces cell death in cultured human embryonic cerebral cortical neurons through N-methyl-D-aspartate receptor activation.

The polyamines putrescine, spermidine, and spermine play important roles in cell proliferation, differentiation, and modulation of ion channel receptors. However, the function of increased concentrations of these compounds in brain injury and disease is unclear, in that they have been proposed as being both neuroprotective and neurotoxic. The effects of spermine and putrescine were studied in human primary cerebral cortical cultures containing both neurons and glia.

Putrescine as a marker of the effects of 2-chloropropionic acid in the rat brain.

The neurotoxin 2-chloropropionic acid (2CPA, 750 mg/kg, per os) induces ataxia in rats causing neuropathological changes (necrosis and edema) localized mainly in the cerebellum (CB). It has been described that putrescine (PUT) is a good marker of severe brain damage. We measured the concentration of PUT (by HPLC) in ataxic rat brains 3 days after 2CPA dosing.

Lesion of substantia nigra pars compacta by the GluR5 agonist ATPA.

Unlabelled: Dopamine (DA) released by substantia nigra pars compacta (SNc) neurons is a key regulator of motor activity. A deficiency in the striatum DA content due to SNc degeneration is a characteristic of Parkinson's disease. The involvement of excitotoxic mechanisms in this pathology has been suggested.

Extracellular putrescine content after acute excitotoxic brain damage in the rat.

We examined the effects of the local infusion of kainic acid (KA), by reverse dialysis in the rat striatum, on the concentration of polyamines in the extracellular striatal compartment and in tissue. KA infusion markedly increased (3-fold) extracellular putrescine (PUT) concentration, which reached its maximum at the end of the dialysis experiments (6 h). Tissue PUT concentration was also increased (2-fold) in the striatum perfused with KA but not in the contralateral side.

Cerebral distribution of polyamines in kainic acid-induced models of status epilepticus and ataxia in rats. Overproduction of putrescine and histological damage.

We study the brain regional distribution of putrescine after excitotoxic damage. After status epilepticus induced by kainic acid (9 mg/kg, i.p.