scholarly journals Angiotensin II Plays a Critical Role in Alcohol-Induced Cardiac Nitrative Damage, Cell Death, Remodeling, and Cardiomyopathy in a Protein Kinase C/Nicotinamide Adenine Dinucleotide Phosphate Oxidase–Dependent Manner

2012 ◽  
Vol 59 (16) ◽  
pp. 1477-1486 ◽  
Author(s):  
Yi Tan ◽  
Xiaokun Li ◽  
Sumanth D. Prabhu ◽  
Kenneth R. Brittian ◽  
Qiang Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Nicotinamide Adenine Dinucleotide ◽  
Critical Role ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Dependent Manner ◽  
Damage Cell ◽  
Kinase C

scholarly journals Mechanism of inhibitory action of TMB-8 [8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate] on aldosterone secretion in adrenal glomerulosa cells

1985 ◽  
Vol 232 (1) ◽  
pp. 87-92 ◽  
Author(s):  
I Kojima ◽  
K Kojima ◽  
H Rasmussen
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Calcium Release ◽  
Calcium Influx ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Aldosterone Secretion ◽  
Kinase C ◽  
Glomerulosa Cells

The mechanism of 8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) action was evaluated in isolated adrenal glomerulosa cells. TMB-8 inhibits both angiotensin II- and K+-stimulated aldosterone secretion in a dose-dependent manner. The ID50 for angiotensin II- and K+-stimulated aldosterone secretion is 46 and 28 microM, respectively. In spite of the fact that 100 microM-TMB-8 inhibits angiotensin II-stimulated aldosterone secretion almost completely, TMB-8 (100 microM) does not inhibit angiotensin II-induced 45Ca2+ efflux from prelabelled cells nor does it affect inositol 1,4,5-trisphosphate-induced calcium release from non-mitochondrial pool(s) in saponin-permeabilized cells. TMB-8 has no inhibitory effect on A23187-induced aldosterone secretion, but 12-O-tetradecanoylphorbol 13-acetate-induced aldosterone secretion is completely abolished. TMB-8 effectively inhibits both angiotensin II- and K+-induced increases in calcium influx but has no effect on A23187-induced calcium influx. TMB-8 inhibits the activity of protein kinase C dose-dependently. These results indicate that TMB-8 inhibits aldosterone secretion without inhibiting mobilization of calcium from an intracellular pool. The inhibitory effect of TMB-8 is due largely to an inhibition of plasma membrane calcium influx, but this drug also inhibits the activity of protein kinase C directly.

scholarly journals Protein Kinase C Epsilon Regulates Mitochondrial Pools of Nampt and NAD Following Resveratrol and Ischemic Preconditioning in the Rat Cortex

2014 ◽  
Vol 34 (6) ◽  
pp. 1024-1032 ◽  
Author(s):  
Kahlilia C Morris-Blanco ◽  
Charles H Cohan ◽  
Jake T Neumann ◽  
Thomas J Sick ◽  
Miguel A Perez-Pinzon
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ischemic Preconditioning ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine ◽  
Dependent Manner ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Resveratrol Treatment ◽  
Kinase C ◽  
Protein Kinase C Epsilon

Preserving mitochondrial pools of nicotinamide adenine dinucleotide (NAD) or nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in NAD production, maintains mitochondrial function and confers neuroprotection after ischemic stress. However, the mechanisms involved in regulating mitochondrial-localized Nampt or NAD have not been defined. In this study, we investigated the roles of protein kinase C epsilon (PKCε) and AMP-activated protein kinase (AMPK) in regulating mitochondrial pools of Nampt and NAD after resveratrol or ischemic preconditioning (IPC) in the cortex and in primary neuronal-glial cortical cultures. Using the specific PKCε agonist ψεRACK, we found that PKCε induced robust activation of AMPK in vitro and in vivo and that AMPK was required for PKCε-mediated ischemic neuroprotection. In purified mitochondrial fractions, PKCε enhanced Nampt levels in an AMPK-dependent manner and was required for increased mitochondrial Nampt after IPC or resveratrol treatment. Analysis of intrinsic NAD autofluorescence using two-photon microscopy revealed that PKCε modulated NAD in the mitochondrial fraction. Further assessments of mitochondrial NAD concentrations showed that PKCε has a key role in regulating the mitochondrial NAD+/nicotinamide adenine dinucleotide reduced (NADH) ratio after IPC and resveratrol treatment in an AMPK- and Nampt-dependent manner. These findings indicate that PKCε is critical to increase or maintain mitochondrial Nampt and NAD after pathways of ischemic neuroprotection in the brain.

A Photodynamic Pathway to Apoptosis Induced by Hypericin in Human Myeloma ARH-77 Cell Line: Possible Relevance to Photodynamic Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5076-5076
Author(s):  
Ferit Avcu ◽  
Ali U. Ural ◽  
Yusuf Baran ◽  
Gungor Sobaci ◽  
Mustafa Deveci ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Line ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Myeloma Cell ◽  
Dependent Manner ◽  
Myeloma Cell Line ◽  
Kinase C

Abstract Hypericin, a photosensitizing plant pigment from Hypericum perforatum, is a protein tyrosine kinase inhibitor that has been exploited in models for anti-tumor and anti-viral activity. In this study, we investigated the effects of hypericin on the human myeloma cell line ARH-77 as a model to determine whether hypericin-induced cell death is available. The cells were incubated with hypericin at concentrations ranging from 0.001 to 10 microg/ml in RPMI at 37°C in 5% CO2 atmosphere for 4 h. Then, the cells were irradiated at 532 nm (fluence=24 J/cm2) using a dye laser pumped by an argon laser (Orion). After 72 h exposure, the IC50 of hypericin was 0.005 microg/ml as determined by the MTT assay. Hypericin exerted phototoxic effect on ARH-77 cells, while it did not produce toxic effect in the absence of irradiation. After 72 h exposure to 0.005 microg/ml photoactive hypericin, apoptosis was assessed by morphological changes, DNA fragmentation and flow cytometric analysis using Annexin V and propidium iodide staining. Most of the cells were accumulated in the late stage of apoptosis and these cells were brightly stained and fragmented nuclei and cytoplasmic blebbing were observed. A decrease in the number of apoptotic cells was detected when protein kinase C was inhibited by addition of staurosporine to photoactive hypericin induced ARH-77 cells. From these results, we demonstrated that exposing myeloma cell line ARH-77 to photoactive hypericin inhibits cell growth in a dose dependent manner, induces apoptotic cell death by protein kinase C activation, and provides a rationale for potential applications in vivo.

Endotoxin-Induced Tissue Factor in Human Monocytes is Dependent upon Protein Kinase C Activation

1993 ◽  
Vol 70 (05) ◽  
pp. 800-806 ◽  
Author(s):  
C Ternisien ◽  
M Ramani ◽  
V Ollivier ◽  
F Khechai ◽  
T Vu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tissue Factor ◽  
Factor Ix ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Kinase C ◽  
Pkc Activation

SummaryTissue factor (TF) is a transmembrane receptor which, in association with factors VII and Vila, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation. The PKC agonists phorbol 12- myristate 13-acetate (PMA) and phorbol 12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes, whereas 4 alpha-12, 13 didecanoate (4 a-Pdd) had no such effect. Both LPS- and PMA-induced TF activity were inhibited, in a concentration dependent manner, by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen determination confirmed that LPS-induced cell-surface TF protein levels decreased in parallel to TF functional activity under staurosporine treatment. Moreover, Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to H7 and staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest of transcription by actinomycin D was not affected by the addition of staurosporine, suggesting that its inhibitory effect occurred at a transcriptional level. We conclude that LPS-induced production of TF and its mRNA by human monocytes are dependent on PKC activation.

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