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J Pharmacol Ther Res 2017 Volume 1 Issue 2
November 02-03, 2017 Chicago, USA
4 th International Congress on
International Conference and Exhibition on
Drug Discovery, Designing and Development
Biochemistry, Molecular Biology: R&D
&
Molecular changes in penumbra after focal photothrombotic stroke in the rat cerebral cortex
Anatoly B Uzdensky and Demyanenko S V
Southern Federal University, Russia
In ischemic stroke cell damage propagates from infarct
core to surrounding tissue. To reveal proteins involved in
neurodegeneration and neuroprotection in penumbra, we
studied biochemical consequences of focal photothrombotic
infarct (PTI) in the rat cerebral cortex. Photosensitizer Bengal
Rose does not cross blood brain barrier and remains in
vasculature. Following laser irradiation induces focal vessel
occlusion and brain cortex infarct. Using proteomic microarrays
“Panorama Ab Microarray, Cell Signaling” and “Panorama
Ab Microarray, Neurobiology” (Sigma-Aldrich), we studied
expression of 448 proteins in penumbra at 1, 4 or 24 hours after
PTI as compared with untreated contralateral cortex. Diverse
cellular subsystems were involved in penumbra response to PTI:
(1) Proteins initiating, regulating or executing various apoptosis
stages (caspases 3, 6, 7, SMAC/DIABLO, Bcl-10, Par4, E2F1,
p75, p38, JNK, p53, NMDAR2a, c-myc); (2) Anti-apoptotic
proteins (Bcl-x, p63, MDM2, p21WAF-1, ERK1/2, ERK5, PKCα,
PKCβ, PKCμ, RAF1, phosphatases 1α and MKP-1, calmodulin,
CaMKIIα, CaMKIV, estrogen and EGF receptors), (3)
Signaling proteins (protein kinases Bα, GSK-3, PKC, DYRK1A,
TDP43, phospholipase Cγ1, S-100, axin1, GSK-3, FRAT1,
NUMB); (4) Proliferation regulators (Cdk6, Cdc7 kinase,
Trf1, topoisomerase-1); (5) Axon outgrowth and guidance
(NAV-3, CRMP2, PKCβ2); (6) Intercellular interactions
(N-cadherin, PMP22); (7) Regulation of actin (cofilin, actopaxin,
p120CTN, α-catenin, p35, neurofilament 68, neurofilament-M,
ezrin, tropomyosin, spectrin (α+β), myosin Va and pFAK)
and microtubule cytoskeleton (βIV-tubulin, polyglutamated
β-tubulin, doublecortin, Tau, MAP1); (8) Vesicular transport and
synaptic transmission (syntaxin-8, TMP21, Munc-18-3, synip,
ALS2, VILIP1, syntaxin, synaptophysin, synaptotagmin, syntaxin,
AP2β/γ, adaptin β1/2); (9) Biosynthesis of neuromediators
(tryptophan hydroxylase, monoamine oxidase B, glutamate
decarboxylase, tyrosine hydroxylase, DOPA decarboxylase,
dopamine transporter); (10) ubiquitin-mediated proteolysis
(ubiquilin-1, UCHL1, NEDD8); (11) Mitochondria quality control
(Pink1, parkin, HtrA2); (12) Cytoprotection (AOP-1, MAKAPK2,
chaperons Hsp70, Hsp90); (13) APP-related proteins (APP,
β-amyloid, nicastrin). These data provide the integral view on
cellular response in penumbra to PTI. They are involved either
in neurodegeneration, or neuroprotection. These changes were
highest at 4 h after PTI and reduced at the next day. Some of
these proteins may serve as potential targets for ischemic
stroke therapy.
Speaker Biography
Anatoly B. Uzdensky is a Professor in Biophysics and the Head of the Laboratory of
Molecular Neurobiology at the Southern Federal University (Rostov-on-Don, Russia).
He is the author of more than 120 journal papers and three books. His current research
interests include stroke and neurotrauma, neurodegeneration and neuroprotection,
cell biology, and proteomics.
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