scholarly journals Cryptococcus neoformansActivates RhoGTPase Proteins Followed by Protein Kinase C, Focal Adhesion Kinase, and Ezrin to Promote Traversal across the Blood-Brain Barrier

2012 ◽  
Vol 287 (43) ◽  
pp. 36147-36157 ◽  
Author(s):  
Jong-Chul Kim ◽  
Benjamin Crary ◽  
Yun C. Chang ◽  
Kyung J. Kwon-Chung ◽  
Kee J. Kim
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Blood Brain Barrier ◽  
Focal Adhesion ◽  
Brain Barrier ◽  
Kinase C ◽  
Blood Brain

The role of protein kinase C in the opening of blood–brain barrier induced by electromagnetic pulse

Toxicology ◽  
2010 ◽  
Vol 273 (1-3) ◽  
pp. 29-34 ◽  
Author(s):  
Lian-Bo Qiu ◽  
Gui-Rong Ding ◽  
Kang-Chu Li ◽  
Xiao-Wu Wang ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Blood Brain Barrier ◽  
Electromagnetic Pulse ◽  
Brain Barrier ◽  
Kinase C ◽  
Blood Brain

Protein kinase C restricts transport of carnitine by amino acid transporter ATB0,+ apically localized in the blood–brain barrier

2014 ◽  
Vol 554 ◽  
pp. 28-35 ◽  
Author(s):  
Katarzyna Michalec ◽  
Caroline Mysiorek ◽  
Mélanie Kuntz ◽  
Vincent Bérézowski ◽  
Andrzej A. Szczepankiewicz ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Amino Acid ◽  
Protein Kinase ◽  
Blood Brain Barrier ◽  
Amino Acid Transporter ◽  
Brain Barrier ◽  
Kinase C ◽  
Blood Brain ◽  
Acid Transporter

scholarly journals Protein kinase C-delta inhibition protects blood-brain barrier from sepsis-induced vascular damage

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Yuan Tang ◽  
Fariborz Soroush ◽  
Shuang Sun ◽  
Elisabetta Liverani ◽  
Jordan C. Langston ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Blood Brain Barrier ◽  
Vascular Damage ◽  
Brain Barrier ◽  
Protein Kinase C Delta ◽  
Kinase C ◽  
Blood Brain

scholarly journals Protein Kinase C Activation Modulates Reversible Increase in Cortical Blood–Brain Barrier Permeability and Tight Junction Protein Expression during Hypoxia and Posthypoxic Reoxygenation

2010 ◽  
Vol 30 (11) ◽  
pp. 1847-1859 ◽  
Author(s):  
Colin L Willis ◽  
Diana S Meske ◽  
Thomas P Davis
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Tight Junction ◽  
Vascular Permeability ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Kinase C ◽  
Blood Brain ◽  
Junction Protein

Hypoxia (Hx) is a component of many disease states including stroke. Ischemic stroke occurs when there is a restriction of cerebral blood flow and oxygen to part of the brain. During the ischemic, and subsequent reperfusion phase of stroke, blood–brain barrier (BBB) integrity is lost with tight junction (TJ) protein disruption. However, the mechanisms of Hx and reoxygenation (HR)-induced loss of BBB integrity are not fully understood. We examined the role of protein kinase C (PKC) isozymes in modifying TJ protein expression in a rat model of global Hx. The Hx (6% O2) induced increased hippocampal and cortical vascular permeability to 4 and 10 kDa dextran fluorescein isothiocyanate (FITC) and endogenous rat-IgG. Cortical microvessels revealed morphologic changes in nPKC-θ distribution, increased nPKC-θ and aPKC-ζ protein expression, and activation by phosphorylation of nPKC-θ (Thr538) and aPKC-ζ (Thr410) residues after Hx treatment. Claudin-5, occludin, and ZO-1 showed disrupted organization at endothelial cell margins, whereas Western blot analysis showed increased TJ protein expression after Hx. The PKC inhibition with chelerythrine chloride (5 mg/kg intraperitoneally) attenuated Hx-induced hippocampal vascular permeability and claudin-5, PKC (θ and ζ) expression, and phosphorylation. This study supports the hypothesis that nPKC-θ and aPKC-ζ signaling mediates TJ protein disruption resulting in increased BBB permeability.

scholarly journals Hydrogen Sulfide Decreases Blood-Brain Barrier Damage via Regulating Protein Kinase C and Tight Junction After Cardiac Arrest in Rats

2018 ◽  
Vol 47 (3) ◽  
pp. 994-1006 ◽  
Author(s):  
Hangbing Li ◽  
Lin Zhu ◽  
Jingwei Feng ◽  
Xiaotong Hu ◽  
Chen Li ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Protein Kinase C ◽  
Hydrogen Sulfide ◽  
Survival Rate ◽  
Protein Kinase ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Brain Barrier ◽  
Kinase C ◽  
Blood Brain

Background/Aims: Hydrogen sulfide (H2S) can decrease blood-brain barrier (BBB) permeability after cardiac arrest (CA) and resuscitation; however, the underlying mechanisms are not understood clearly. Methods: We investigated the effects of inhalation of H2S on CA and resuscitation in a rat model of CA. We used Evans blue to detect the integrity of BBB and Western blot to assess the activation of protein kinase c (PKC) isozymes and the expression of Claudin-5, Occludin, and ZO-1. Neurological deficit scales and the 14-days survival rate were measured. Results: We determined that inhalation of 40 p.p.m or 80 p.p.m H2S significantly decreased brain water content and Evans blue leakage, ameliorated neurologic deficit scale and improved 14-days survival rate. H2S inhibited the activation of PKC-α, β I, β II and δ, impelled the activation of PKC-ε, and increased the expression of Claudin-5, Occludin and ZO-1. Conclusions: H2S improved the integrity of BBB, mitigated brain edema; improved neurological outcome and 14-days survival rate in rats after CA and resuscitation. The beneficial effects of H2S may be associated with inhibiting the activation of PKC-α, β I, β II and δ, promoting the activation of PKC-ε, and increasing the expression of Claudin-5, Occludin and ZO-1.

scholarly journals DIPG-29. PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE 3-KINASE (PI3K) INHIBITION DRIVES PROTEIN KINASE C ACTIVATION (PKC) IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii292-iii293
Author(s):  
Ryan J Duchatel ◽  
Abdul Mannan ◽  
Evangeline R Jackson ◽  
Dilana Staudt ◽  
David A Skerrett-Byrne ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Blood Brain Barrier ◽  
Cellular Migration ◽  
Brain Barrier ◽  
Mtor Inhibition ◽  
Kinase C ◽  
Blood Brain ◽  
Pi3k Inhibition ◽  
Pkc Signaling

Abstract Recurring somatic mutations and gene amplifications to members of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling axis are overarching contributors to the aggressive growth and survival of diffuse intrinsic pontine gliomas (DIPG). However, targeting PI3K has thus far failed to improve outcomes for patients in the clinic. To identify the mechanisms underpinning PI3K/AKT/mTOR treatment failure in DIPG, we have employed high-resolution quantitative phosphoproteomic profiling in patient-derived DIPG cell lines harboring H3K27M and PI3K mutations, +/- the blood-brain barrier permeable PI3K inhibitor, paxalisib (previously “GDC-0084”, currently in Phase I trials - NCT03696355) and rapamycin. Paxalisib was significantly more potent than rapamycin at inducing PI3K/AKT/mTOR inhibition, however, both simultaneously activated protein kinase C signaling (pT500PKCβ +8.2 and +4.5 fold, respectively). PKC lies directly upstream of myristoylated alanine-rich C-kinase substrate (MARCKs), which was phosphorylated at Ser170 by +9.4 and +4.7 fold, respectively; promoting actin cytoskeletal remodeling and cellular migration. Indeed, activation of PKC signaling using phorbol 12-myristate 13-acetate (PMA), increased DIPG cell growth and migration by >3 fold. Targeting PKC using midostaurin (FDA-approved for acute myeloid leukemia), and enzastaurin (blood-brain barrier penetrant inhibitor of PKCβ), in combination with paxalisib was highly synergistic (CI=<0.9), reducing proliferation and driving apoptosis. Mechanistically, compensatory activation of PKC signaling following PI3K inhibition was regulated by the accumulation of Ca+2 ions, as chelation using BAPTA-AM significantly reduced PKC activity following PI3K inhibition. These data highlight the power of phosphoproteomic profiling for the rational design of drug combination strategies, which need to be tested in vivo prior to clinical trials for DIPG.

scholarly journals Involvement of Focal Adhesion Kinase inEscherichia coli Invasion of Human Brain Microvascular Endothelial Cells

2000 ◽  
Vol 68 (11) ◽  
pp. 6423-6430 ◽  
Author(s):  
Marpadga A. Reddy ◽  
Carol A. Wass ◽  
Kwang Sik Kim ◽  
David D. Schlaepfer ◽  
Nemani V. Prasadarao
Keyword(s):  
Endothelial Cells ◽  
Focal Adhesion Kinase ◽  
Tyrosine Phosphorylation ◽  
Blood Brain Barrier ◽  
Focal Adhesion ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
E Coli ◽  
Blood Brain

ABSTRACT Escherichia coli K1 traversal across the blood-brain barrier is an essential step in the pathogenesis of neonatal meningitis. We have previously shown that invasive E. colipromotes the actin rearrangement of brain microvascular endothelial cells (BMEC), which constitute a lining of the blood-brain barrier, for invasion. However, signal transduction mechanisms involved in E. coli invasion are not defined. In this report we show that tyrosine kinases play a major role in E. coli invasion of human BMEC (HBMEC). E. coli induced tyrosine phosphorylation of HBMEC cytoskeletal proteins, focal adhesion kinase (FAK), and paxillin, with a concomitant increase in the association of paxillin with FAK. Overexpression of a dominant interfering form of the FAK C-terminal domain, FRNK (FAK-related nonkinase), significantly inhibited E. coli invasion of HBMEC. Furthermore, we found that FAK kinase activity and the autophosphorylation site (Tyr397) are important in E. coli invasion of HBMEC, whereas the Grb2 binding site (Tyr925) is not required. Immunocytochemical studies demonstrated that FAK is recruited to focal plaques at the site of bacterial entry. Consistent with the invasion results, overexpression of FRNK, a kinase-negative mutant (Arg454 FAK), and a Src binding mutant (Phe397 FAK) inhibited the accumulation of FAK at the bacterial entry site. The overexpression of FAK mutants in HBMEC also blocked theE. coli-induced tyrosine phosphorylation of FAK and its association with paxillin. These observations provide evidence that FAK tyrosine phosphorylation and its recruitment to the cytoskeleton play a key role in E. coli invasion of HBMEC.

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