PKC-<i>β</i>Exacerbates<i>in vitro</i>Brain Barrier Damage in Hyperglycemic Settings via Regulation of RhoA/Rho-kinase/MLC2 Pathway

Srivastava, Kirtiman; Shao, Beili; Bayraktutan, Ulvi

doi:10.1038/jcbfm.2013.151

Cited by 56 publications

(49 citation statements)

References 37 publications

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“…showed that PKC-β and PKC-β II in human BMECs were activated after exposure to high glucose in an in vitro BBB model, and the activated PKC inhibited the expression of Occludin and undermined the integrity of BBB. Similar result was confirmed by transfecting BMECs with siRNA targeting PKC-β, in which the activation of PKC-β was impeded and the BBB damage was mitigated [35]. A recent study demonstrated that Go6983 decreased the phosphorylation levels of PKCδ and inhibited the release of MMP-9, which suggested that PKC-δ participated in PAR1-mediated MMP-9 release from pericytes, which lead to BBB dysfunction [40].…”

Section: Cellular Physiology and Biochemistrysupporting

confidence: 59%

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

Zhu

Feng

et al. 2018

Cell Physiol Biochem

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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.

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Section: Cellular Physiology and Biochemistrysupporting

confidence: 59%

“…Previous studies have confirmed that the activation of PKC is the major factor in CIRI [5,8,[35][36][37][38]. As previously reported, hypoxia-induced BBB permeability changes occur via a Cellular Physiology and Biochemistry…”

Section: Discussionmentioning

confidence: 49%

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

Zhu

Feng

et al. 2018

Cell Physiol Biochem

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“…The protein levels of FAK, p63 (4A4), MMP1, MMP2, BrdU (Santacruz Biotech), Src, pFAK-Y 395 , MMP14 (Abcam), paxillin (BD biosciences), pPaxillin-Y 118 , pFAK-Y 576/577 , pSrc-Y 496 , pAKT-S 493 , total AKT, p-c-jun-S 73 , c-Jun (Cell Signaling) and β-actin (Sigma-aldrich) were detected in whole cell lysates by immunoblotting as previously described [50]. …”

Section: Methodsmentioning

confidence: 99%

p63 drives invasion in keratinocytes expressing HPV16 E6/E7 genes through regulation of Src-FAK signalling

et al. 2015

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Using microarray information from oro-pharyngeal data sets and results from primary human foreskin keratinocytes (HFK) expressing Human Papilloma Virus (HPV)-16 E6/E7 proteins, we show that p63 expression regulates signalling molecules which initiate cell migration such as Src and focal adhesion kinase (FAK) and induce invasion in 3D-organotypic rafts; a phenotype that can be reversed by depletion of p63. Knockdown of Src or FAK in the invasive cells restored focal adhesion protein paxillin at cell periphery and impaired the cell migration. In addition, specific inhibition of FAK (PF573228) or Src (dasatinib) activities mitigated invasion and attenuated the expression/activity of matrix metalloproteinase 14 (MMP14), a pivotal MMP in the MMP activation cascade. Expression of constitutively active Src in non-invasive HFK expressing E6/E7 proteins upregulated the activity of c-Jun and MMP14, and induced invasion in rafts. Depletion of Src, FAK or AKT in the invasive cells normalised the expression/activity of c-Jun and MMP14, thus implicating the Src-FAK/AKT/AP-1 signalling in MMP14-mediated extra-cellular matrix remodelling. Up-regulation of Src, AP-1, MMP14 and p63 expression was confirmed in oro-pharyngeal cancer. Since p63 transcriptionally regulated expression of many of the genes in this signalling pathway, it suggests that it has a central role in cancer progression.

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“…PKCβ, in particular, quickly increases the RhoA/myosin-regulated light chain 2 pathway leading to increased brain edema following stroke [80]. Some isoforms are unable to translocate following ischemic injury and trigger intracellular pathways that contribute to neuronal death or injury [81].…”

Section: Pkc and Strokementioning

confidence: 99%

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

Lucke‐Wold

Turner

Logsdon

et al. 2014

JAD

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Ischemic stroke and Alzheimer’s disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood-brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-β toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury.

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PKC-βExacerbatesin vitroBrain Barrier Damage in Hyperglycemic Settings via Regulation of RhoA/Rho-kinase/MLC2 Pathway

Cited by 56 publications

References 37 publications

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

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

p63 drives invasion in keratinocytes expressing HPV16 E6/E7 genes through regulation of Src-FAK signalling

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

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