PDT-induced epigenetic changes in the mouse cerebral cortex: A protein microarray study

Demyanenko, Svetlana; Uzdensky, Anatoly B.; Sharifulina, Svetlana; Lapteva, T.O.; Polyakova, L.P.

doi:10.1016/j.bbagen.2013.09.014

Cited by 22 publications

(17 citation statements)

References 54 publications

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“…β-Amyloid is produced from amyloid precursor protein (APP) by TMP21, a member of the presenilin complex [42]. The observed accumulation of β-amyloid peptide (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) in penumbra could be also neurotoxic.…”

Section: Discussionmentioning

confidence: 99%

“…Although the mean experiment/control ratios significantly differed from 1 (p < 0.05), only >30 % differences (the cut-off level) in the protein levels between irradiated and control animals (i.e., experimental/control ratios > 1.3) are displayed in Table 2 and discussed. The reliability of the proteomic microarray data was provided by the self-control experiment using the swapped staining in the second microarray [19,21].…”

Section: Proteomic Studymentioning

confidence: 99%

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Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

et al. 2016

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After ischemic stroke, cell damage propagates from infarct core to surrounding tissues (penumbra). To reveal proteins involved in neurodegeneration and neuroprotection in penumbra, we studied protein expression changes in 2-mm ring around the core of photothrombotic infarct induced in the rat brain cortex by local laser irradiation after administration of Bengal Rose. The ultrastructural study showed edema and degeneration of neurons, glia, and capillaries. Morphological changes gradually decreased across the penumbra. Using the antibody microarrays, we studied changes in expression of >200 neuronal proteins in penumbra 4 or 24 h after focal photothrombotic infarct. Diverse cellular subsystems were involved in the penumbra tissue response: signal transduction pathways such as protein kinase Bα/GSK-3, protein kinase C and its β1 and β2 isoforms, Wnt/β-catenin (axin1, GSK-3, FRAT1), Notch/NUMB, DYRK1A, TDP43; mitochondria quality control (Pink1, parkin, HtrA2); ubiquitin-mediated proteolysis (ubiquilin-1, UCHL1); axon outgrowth and guidance (NAV-3, CRMP2, PKCβ2); vesicular trafficking (syntaxin-8, TMP21, Munc-18-3, synip, ALS2, VILIP1, syntaxin, synaptophysin, synaptotagmin); biosynthesis of neuromediators (tryptophan hydroxylase, monoamine oxidase B, glutamate decarboxylase, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter); intercellular interactions (N-cadherin, PMP22); cytoskeleton (neurofilament 68, neurofilament-M, doublecortin); and other proteins (LRP1, prion protein, β-amyloid). These proteins are involved in neurodegeneration or neuroprotection. Such changes were most expressed 4 h after photothrombotic impact. Immunohistochemical and Western blot studies of expression of monoamine oxidase B, UCHL1, DYRK1A, and Munc-18-3 confirmed the proteomic data. These data provide the integral view on the penumbra response to photothrombotic infarct. Some of these proteins can be potential targets for ischemic stroke therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Proteomic Studymentioning

confidence: 99%

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

et al. 2016

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“…Other studies found similar increases in ALA‐S activity in response to both chronic and acute alcohol in leukocytes from human blood samples (McColl et al., , ). Increases in peripheral ALA have been shown to increase brain levels of PPIX 2.5‐fold in the mouse cortex (Demyanenko, Uzdensky, Sharifulina, Lapteva, & Polyakova, ). Clinically, oral administration of ALA is used to delineate gliomas via the fluorescent properties of PPIX, which gliomas accumulate in greater amounts than non‐malignant brain tissue (Stepp & Stummer, ), providing evidence that in humans increases in ALA lead to elevations of PPIX.…”

Section: Discussionmentioning

confidence: 99%

Detecting neuroinflammation in the brain following chronic alcohol exposure in rats: A comparison between in vivo and in vitro TSPO radioligand binding

Tyler

Kim

Guo

et al. 2019

Eur J of Neuroscience

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Excessive alcohol consumption is associated with neuroinflammation, which likely contributes to alcohol‐related pathology. However, positron emission tomography (PET) studies using radioligands for the 18‐kDa translocator protein (TSPO), which is considered a biomarker of neuroinflammation, reported decreased binding in alcohol use disorder (AUD) participants compared to controls. In contrast, autoradiographic findings in alcohol exposed rats reported increases in TSPO radioligand binding. To assess if these discrepancies reflected differences between in vitro and in vivo methodologies, we compared in vitro autoradiography (using [3H]PBR28 and [3H]PK11195) with in vivo PET (using [11C]PBR28) in male, Wistar rats exposed to chronic alcohol‐vapor (dependent n = 10) and in rats exposed to air‐vapor (nondependent n = 10). PET scans were obtained with [11C]PBR28, after which rats were euthanized and the brains were harvested for autoradiography with [3H]PBR28 and [3H]PK11195 (n = 7 dependent and n = 7 nondependent), and binding quantified in hippocampus, thalamus, and parietal cortex. Autoradiography revealed significantly higher binding in alcohol‐dependent rats for both radioligands in thalamus and hippocampus (trend level for [3H]PBR28) compared to nondependent rats, and these group differences were stronger for [3H]PK11195 than [3H]PBR28. In contrast, PET measures obtained in the same rats showed no group difference in [11C]PBR28 binding. Our in vitro data are consistent with neuroinflammation associated with chronic alcohol exposure. Failure to observe similar increases in [11C]PBR28 binding in vivo suggests the possibility that a mechanism mediated by chronic alcohol exposure interferes with [11C]PBR28 binding to TSPO in vivo. These data question the sensitivity of PBR28 PET as a methodology to assess neuroinflammation in AUD.

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“…Epigenetic processes include DNA methylation and demethylation, and modifications on histones, including methylation/demethylation, phosphorylation/dephosphorylation and acetylation/deacetylation. These processes regulate the RNA polymerase activity and control the access of transcription factors to gene promoters thus affecting gene expression 190 . DNA methylation and histone modifications can be easily targeted and reversed by drugs, which has led to their investigation as possible clinical therapies 191-193 .…”

Section: Epigenetic Reversalmentioning

confidence: 99%

T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?

Anzengruber

Avci

Freitas

et al. 2015

Photochem Photobiol Sci

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Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naïve mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients.

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PDT-induced epigenetic changes in the mouse cerebral cortex: A protein microarray study

Cited by 22 publications

References 54 publications

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

Detecting neuroinflammation in the brain following chronic alcohol exposure in rats: A comparison between in vivo and in vitro TSPO radioligand binding

T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?

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