Science

ACTIVATION OF PKC ISOFORM Β1 AT THE BLOOD–BRAIN BARRIER RAPIDLY DECREASES P-GLYCOPROTEIN ACTIVITY AND ENHANCES DRUG DELIVERY TO THE BRAIN

P-glycoprotein is an ATP (adenosine triphosphate)-driven drug efflux transporter that is highly expressed at the blood brain barrier (BBB) and is a major obstacle to the pharmacotherapy of central nervous system diseases, including brain tumors, neuro-AIDS, and epilepsy. Previous studies have shown that P-glycoprotein transport activity in…
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ROLE OF ERK1/2 MAPK SIGNALING IN THE MAINTENANCE OF MYELIN AND AXONAL INTEGRITY IN THE ADULT CNS

Oligodendrocytes form myelin during postnatal development and then maintain a functional myelin sheath throughout adult life. While many regulators of developmental myelination have been identified, the signal transduction mechanisms that regulate oligodendrocyte functions in adulthood are not well understood. The extracellular signal-regulated kinases-1 and -2 (ERK1/2), downstream mediators of mitogen-activated protein kinases (MAPKs), have emerged as prominent…
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NEUROINFLAMMATION AND NON-MOTOR SYMPTOMS: THE DARK PASSENGER OF PARKINSON’S DISEASE?

Generally speaking, inflammation as a key piece to the Parkinson’s disease (PD) puzzle is a relatively new concept. Acceptance of this concept has gained ground as studies by various researchers have demonstrated the potential of mitigating nigral cell death by curtailing inflammation in animal models of PD. We propose that the significance of inflammation in PD pathology may extend beyond the nigrostriatal region. In the current review, we present an argument for this based on the Braak staging and discuss how inflammation might contribute to the development of non-motor PD symptoms…
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THE PROTEIN KINASE C ACTIVATOR PHORBOL MYRISTATE ACETATE DECREASES BRAIN EDEMA BY AQUAPORIN 4 DOWNREGULATION AFTER MIDDLE CEREBRAL ARTERY OCCLUSION IN THE RAT

The protein kinase C activator phorbol12-myristate13-acetate (PMA) is known to interact with aquaporin4 (AQP4),a water-selective transporting protein that is abundant in astrocytes, and has experimentally been found to decrease osmotically-induced cell swelling. The purpose of this study was to examine whether PMA reduces brain edema following focal ischemia induced by middle cerebral artery (MCA) occlusion by modulation of AQP4 expression. Male Sprague-Dawley rats were randomly assigned to…
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PROTEIN KINASE C Δ ACTIVATES THE MEK-ERK PATHWAY IN A MANNER INDEPENDENT OF RAS AND DEPENDENT ON RAF*

Although the involvement of protein kinase C (PKC) in the activation of the mitogen activated protein (MAP) kinase pathway has been implicated through experiments using 12-O-tetradecanoylphorbol 13 acetate (TPA), there has been no direct demonstration that PKC activates the MAP kinase pathway. A Raf-dependent intact cell assay system for monitoring the activation of MAPK/ERK kinase (MEK) and extracellular signal related kinase (ERK) permitted us to evaluate the role of PKC isotypes in MAP kinase activation. Treatment of cells with TPA or epidermal growth factor resulted in the activation of MEK and ERK…
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PROTEIN KINASE C Δ INDUCES SRC KINASE ACTIVITY VIA ACTIVATION OF THE PROTEIN TYROSINE PHOSPHATASE PTPΑ*

Previously we have shown that protein kinase C (PKC)-mediated reorganization of the actin cytoskeleton in smooth muscle cells is transmitted by the non-Receptor tyrosine kinase, Src. Several authors have described how 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation of cells results in an increase of Src activity, but the mechanism of the PKC-mediated Src activation is…
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ACTIVATION OF PROTEIN KINASE C ALPHA IS REQUIRED FOR TPA-TRIGGERED ERK (MAPK) SIGNALING AND GROWTH INHIBITION OF HUMAN HEPATOMACELL HEPG2

The signaling mechanisms for most of the antiproliferative processes are not fully understood. We have demonstrated that ERK(MAPK) signaling was involved in the induction of both p15INK4b and p16INK4a CDK inhibitors and growth inhibition of hepatoma cell Hep G2 triggered by the tumor promoter tetra-decanoylphorbolacetate (TPA).In this study, the upstream signal mechanism for TPA-induced ERK (MAPK) activation was investigated. In Hep G2 cells only one of the…
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SUSTAINED ACTIVATION OF ERK1/2 MAPK IN OLIGODENDROCYTES AND SCHWANN CELLS ENHANCES MYELIN GROWTH AND STIMULATES OLIGODENDROCYTE PROGENITOR EXPANSION

Myelin is a biologically active membrane receiving and processing signals from axons. Although much is known about its structure and molecular composition, the intracellular signal transduction pathways, active during specific phases of myelinogenesis for regulating myelin formation, remain poorly understood. Recent genetic loss-of-function studies have suggested a key role of…
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