Результаты поиска

Glucocorticoid inhibition of Na-Pi cotransport in renal epithelial cells is mediated by protein kinase C.

The effect and mechanism of action of glucocorticoids (GC) on Na-Pi cotransport were evaluated in opossum kidney cells. Dexamethasone (1-100 … ory effects on Pi uptake. Staurosporine, GF109203X, or calphostin C (three dissimilar inhibitors of protein kinase C (PKC)) and PKC down-regulation blunted the inhibitory effect of glucocorticoids on Pi uptake. GC increased both membrane-bound PKC activity and the membrane/cytosol PKC activity ratio. This is the first report of GC activation of PKC in renal cells, …

Attenuation of ultraviolet radiation-induced edema and erythema with topical calmodulin and protein kinase C inhibitors.

We treated Skh:HR1 hairless albino mice, NSA mice and hairless albino guinea pigs topically with N-(6-aminohexyl)-5-chloro-1-naphthalenesulf … lude that neither are physical or chemical sunscreens. These results suggest that calmodulin and/or protein kinase C-dependent events are involved in manifesting some of the effects of UV irradiation on skin.

Alterations in protein kinase C activity and membrane lipid metabolism in cerebral vasospasm after subarachnoid hemorrhage.

Changes in protein kinase C (PKC) activity, membrane lipid metabolism, and the extent of 20-kDa myosin light chain (MLC) phosphorylation in spastic cerebral basilar arteries were examined by using the beagle "two-hemorrhage" model of subarachnoid hemorrhage. In spastic arteries at days 4 and 7, cytosolic PKC activity showed a decrease of 40-45% with no significant changes in membrane PKC activity as compared with nonspastic control arteries. Cytosolic PKC activity of the day 14 arteries returned toward the normal control level with the remission of vasospasm. Western blot analysis of the PKC i…

Shear stress regulates endothelin-1 release via protein kinase C and cGMP in cultured endothelial cells.

The effect of shear stress on the release of endothelin-1 (ET-1) from endothelial cells is at present controversial with various investigato … blocked the stimulation in both cases, suggesting that ET-1 release is increased via activation of protein kinase C (PKC). Exposure to 6-25 dyn/cm2 for > or = 6 h dramatically inhibited ET-1 release and led to 0-70% inhibition of cumulative release by 16 h. Pretreatment with N omega-nitro-L-arginine (L-NNA) reversed this suppression in a dose-dependent manner, im …

Protein kinase C activation and protooncogene expression in differentiation/retrodifferentiation of human U-937 leukemia cells.

Human U-937 leukemia cells differentiate along the monocytic lineage following 3-day exposures to 12-O-tetradecanoylphorbol-13-acetate (TPA) … observed in uninduced cells. Treatment of U-937 cells with TPA resulted in a rapid translocation of protein kinase C (PKC) from the cytosol to cell membrane fractions within 2-8 min. Increased levels of membrane-associated PKC activity persisted until 17-29 days. However, longer periods of incubation were associated with a return to the distribution of PKC in cont …

Negative feedback mechanisms: evidence that desensitization of pineal alpha 1-adrenergic responses involves protein kinase-C.

alpha 1-Adrenergic stimulation of the pinealocyte translocates protein kinase-C, which, in turn, has an important positive effect on pineal cell function; translocation amplifies beta-adrenergic stimulation of both cAMP and cGMP. In the present report negative feedback effects of protein kinase-C are described, including inhibition of alpha 1-adrenergically induced increases in cytosolic Ca2+ ([Ca2+]i), phosphatidylinositol hydrolysis, and cGMP in beta-adrenergically stimulated cells. Time-course studies of cGMP and [Ca2+]i responses indicated that the onset of inhibition by the protein kinase

Sphingosine and psychosine, suggested inhibitors of protein kinase C, inhibit LH effects in rat luteal cells.

The possible involvement of protein kinase C on luteinizing hormone (LH) effects in dispersed rat luteal cells was investigated using two substances that have been reported to be protein kinase C inhibitors, sphingosine and psychosine. Sphingosine efficiently inhibited protein kinase C activity both in brain and luteal cytosol fractions. Both substances inhibited LH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in a dose-dependent fashion with an LD50 at 3-7 microM (sphingosine) and 40 microM (psychosine). LH-stimulated progesterone production was also inhibited with an ID50 at…

Possible involvement of direct stimulation of protein kinase C by unsaturated fatty acids in platelet activation.

Arachidonate and other unsaturated fatty acids stimulated platelet protein kinase C in a dose-dependent manner (5-50 micrograms/ml), when the activity was assayed with either isolated substrates or the platelet cytosol. When human platelets were stimulated by arachidonate, two types of platelet activation were observed. Platelet activation induced by a low level of arachidonate (0.1-5 micrograms/ml) was inhibited by aspirin, but activation induced by a high level of arachidonate (10-50 micrograms/ml) was not. These activations were associated with the phosphorylation of 40K and 20K proteins. O…

Cytoskeletal reorganization evoked by Rho-associated kinase- and protein kinase C-catalyzed phosphorylation of cofilin and heat shock protein 27, respectively, contributes to myogenic constriction of rat cerebral arteries.

Our understanding of the molecular events contributing to myogenic control of diameter in cerebral resistance arteries in response to changes in intravascular pressure, a fundamental mechanism regulating blood flow to the brain, is incomplete. Myosin light chain kinase and phosphatase activities are known to be increased and decreased, respectively, to augment phosphorylation of the 20-kDa regulatory light chain subunits (LC20) of myosin II, which permits cross-bridge cycling and force development. Here, we assessed the contribution of dynamic reorganization of the actin cytoskeleton and thin

Protein kinase C iota facilitates insulin-induced glucose transport by phosphorylation of soluble nSF attachment protein receptor regulator (SNARE) double C2 domain protein b.

AIMS/INTRODUCTION: Double C2 domain protein b (DOC2b), one of the synaptotagmins, has been shown to translocate to the plasma membrane, and to initiate membrane-fusion processes of vesicles containing glucose transporter 4 proteins on insulin stimulation. However, the mechanism by which DOC2b is regulated remains unclear. Herein, we identified the upstream regulatory factors of DOC2b in insulin signal transduction. We also examined the role of DOC2b on systemic homeostasis using DOC2b knockout (KO) mice. MATERIALS AND METHODS: We first identified DOC2b binding proteins by immunoprecipitation

Protein kinase C-λ drives third-degree burn-induced muscle wasting via STAT3-dependent catabolic pathways.

OBJECTIVE: Severe burn injury triggers profound skeletal muscle atrophy through incompletely understood molecular mechanisms. This study investigated the role of protein kinase C (PKC) isoforms in burn-induced muscle wasting and evaluated potential therapeutic targets. METHODS: We examined PKC isoform expression in skeletal muscle biopsies from burn patients with second-degree (n = 5) and third-degree burns (n = 5) at 7 days post-injury. Mouse burn models were established to investigate PKC signaling at 14 days post-injury. Muscle-specific PKC-lambda (PKC-λ) knockout mice and pharmacological …

Протеиновая киназа C Modolor bryosstatin-1 в терапевтическом порядке направлена на уменьшение нейроинфламмации и поощрение ремиэлизации.

В множестве склерозов (MS) микроглиа и макрофаги в центральной нервной системе (CNS) играют важную роль в определении баланса между демиелинацией, нейродегенерацией и ремонтом миелина. Фагоцитичные и регенерационные функции этих врожденных иммунных клеток поддерживают ремиелионацию, в то время как хроническая и неадаптационная провокационная активация способствует расширению масштабов поражения и инвалидности, особенно в прогрессивных формах MS. В настоящее время ни одно из утвержденных лекарственных средств не нацелено на микроглию и макрофаги в рамках ЦНС, что ведет к отсутствию методов лече

Совпадение в аннотации оригинала
In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining the bala … ting remyelination and slowing disease progression for individuals with MS. Here, we found that the protein kinase C (PKC)-modulating drug bryostatin-1 (bryo-1), a CNS-penetrant compound with an established human safety profile, shifts the transcriptional programs of microglia and CNS-associated macrophages from a proinflammatory phenotype to a regenerative phenot …

Filamin A regulates caspase-3 cleavage in platelets in a protein kinase C (PKC)-dependent manner.

Apoptosis is a critical process for the maintenance of cell populations, and involves mitochondrial depolarization, the sequential cleavage … ) but these effects were essentially abrogated in FLNA-null platelets (platelet-specific knockout). Protein kinase C (PKC), a known FLNA ligand, was also activated by ABT-737, and PKC's phosphorylation of its downstream substrates was attenuated in FLNA-null platelets. The PKC inhibitor bisindolylmaleimide (BIM) also reduced caspase-3 cleavage, thus essentially ph …

Berberine Reverses Nitroglycerin Tolerance through Suppressing Protein Kinase C Alpha Activity in Vascular Smooth Muscle Cells.

PURPOSE: The aim of this study was to evaluate the effects of berberine on nitroglycerin (NTG) tolerance and explore the underlying mechanis … with an NTG patch in vivo was reversed by co-treatment with berberine, as well as the inhibitors of protein kinase C (PKC) and protein kinase C alpha (PKCα). The mechanistic study revealed that PKCα participated in the development of NTG tolerance as NTG increased the activity of PKCα with enriched PKCα membrane localization and elevated phosphorylation of PKCα in …

Involvement of protein kinase C beta1-serotonin transporter system dysfunction in emotional behaviors in stressed mice.

Selective serotonin reuptake inhibitors are the first-line antidepressants for treating major depressive and post-traumatic stress disorders. These inhibitors directly bind to the serotonin transporter (SERT). Protein kinase C (PKC) is a key regulator of SERT functions as it can attenuate SERT activity through phosphorylation and its subsequent internalization. However, whether PKC-regulated SERT functions are involved in emotional impairment in a mouse model of stress remains unclear. Using a mouse model of swim-induced stress, we investigated whether the PKC-SERT system is involved in emotio…

Genetic Reduction in Left Ventricular Protein Kinase C-α and Adverse Ventricular Remodeling in Human Subjects.

BACKGROUND: Inhibition of PKC-α (protein kinase C-α) enhances contractility and cardioprotection in animal models, but effects in humans are unknown. Genotypes at rs9912468 strongly associate with PRKCA expression in the left ventricle, enabling genetic approaches to measure effects of reduced PKC-α in human populations. METHODS AND RESULTS: We analyzed the cis expression quantitative trait locus for PRKCA marked by rs9912468 using 313 left ventricular specimens from European Ancestry patients. The forward strand minor allele (G) at rs9912468 is associated with reduced PKC-α transcript abunda…

Phorbol 12,13-dibutyrate-induced protein kinase C activation triggers sustained contracture in human myometrium in vitro.

BACKGROUND: Although physiologic transition from rhythmic contractions to uterine retraction postpartum remains a poorly understood process, it has been shown that the latter is essential in the prevention of hemorrhage and its negative consequences. OBJECTIVE: To investigate the transition from oscillatory contractions to tonic contracture in human myometrium after delivery, a mechanism purported to facilitate postpartum hemostasis. Protein kinase C (PKC) plays a key regulatory role in human uterine contractions because it can prevent dephosphorylation of regulatory proteins and sensitize th…

Macropinocytosis of type XVII collagen induced by bullous pemphigoid IgG is regulated via protein kinase C.

Macropinocytosis is an endocytic pathway that is involved in the nonselective fluid uptake of extracellular fluid. Bullous pemphigoid (BP) i … verabundant phosphorylation of COL17. The overabundant phosphorylation of COL17 was suppressed by a protein kinase C (PKC) inhibitor. In addition, PKC inhibitor repressed COL17 endocytosis using cell culture and organ culture systems. Finally, the depletion of COL17 was not observed in the HEK293 cells transfected COL17 without intracellular domain. These results …

Protein kinase C-activating tumor promoters modulate the DNA damage response in UVC-irradiated TK6 cells.

12-O-Tetradecanoylphorbol-13-acetate (TPA) is a non-genotoxic tumor promoter that dysregulates the protein kinase C (PKC) pathway and causes variable cellular responses to DNA damage in different experimental models. In the present study, we pretreated human lymphoblastoid TK6 cells (wild-type p53) for 72 h with TPA, and five other PKC-activating tumor promoters, to determine how sustained exposure to these chemicals modulates key DNA damage response (DDR) endpoints induced by UVC-irradiation. Here we show that pre-treatment with PKC-activating tumor promoters augmented the sensitivity of TK6 …

FGF-2 protects cardiomyocytes from doxorubicin damage via protein kinase C-dependent effects on efflux transporters.

AIMS: The anti-cancer anthracycline doxorubicin (DOX) increases the risk of cardiac damage, indicating a need to protect the heart and still … neficial effect of FGF-2 against cell damage and increased transporter RNA levels were blunted with protein kinase C (PKC) inhibition. Finally, FGF-2 stimulated efflux transport of calcein and DOX, and treatment with efflux transporter inhibitors significantly attenuated the protective effect of FGF-2 from DOX-induced injury. CONCLUSION: Administered FGF-2 increa …