scholarly journals Role of Protein Kinase C in the Expression of Endothelin Converting Enzyme-1

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1440-1449 ◽  
Author(s):  
Mogher Khamaisi ◽  
Rachel Dahan ◽  
Saher Hamed ◽  
Zaid Abassi ◽  
Samuel N. Heyman ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Converting Enzyme ◽  
Endothelin 1 ◽  
Kinase C ◽  
Endothelin Converting Enzyme ◽  
Related Increase

Increased expression of endothelin converting enzyme-1 (ECE-1) is associated with diabetic nephropathy. The molecular mechanisms underlying this association, as yet unknown, possibly involve protein kinase C (PKC) pathways. In the present study, we examined the effects of high glucose and PKC activation on ECE-1 expression in primary human umbilical vein endothelial cells (HUVECs) and in HUVEC line (EA.hy926). Increasing glucose concentration, but not mannitol, from 5.5–22.2 mmol/liter for 3 d, enhanced prepro endothelin-1 (ET-1) mRNA expression, ET-1 levels, ECE-1 protein, and mRNA expressions by 7, 4, 20, and 2.6-fold, respectively. High glucose increased ECE-1 protein expression dose and time dependently. By Western blot analysis, PKC-β1, -β2, and -δ isoform levels were significantly increased relative to other isoforms when glucose level was increased. Treatment with Rottlerin, a PKC-δ isoform inhibitor, reduced significantly the glucose-induced ET-1 secretion, and ECE-1 protein expression, but (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16,21-dimetheno 1H,13H-dibenzo[e,k]pyrrolo[3,4-h] (1, 4, 3) oxadiaza-cyclohexadecene-1,3(2H)-dione or Gö6976, specific PKC-β and -α inhibitors, respectively, did not. Overexpression of PKC-δ but not PKC-α or -β1 isoforms by adenovirus vector containing the respective cDNA in HUVECs incubated with 5.5 mmol/liter glucose, increased in parallel PKC proteins, and glucose-induced endothein-1 and ECE-1 protein expression by 4- to 6-fold. These results show that enhanced ECE-1 expression induced by hyperglycemia is partly due to activation of the PKC-δ isoform. Thus, inhibition of this PKC isoform may prevent diabetes-related increase in ET-1. Hyperglycemia-induced enhanced endothelin converting enzyme-1 expression is mediated by PKC-δ. Inhibition of this PKC isoform may prevent diabetes-related increase in endothelin-1.

scholarly journals High glucose alters the response of mesangial cell protein kinase C isoforms to endothelin-1

1999 ◽  
Vol 55 (2) ◽  
pp. 486-499 ◽  
Author(s):  
Emily ANNE Glogowski ◽  
Evangelia Tsiani ◽  
Xiaopeng Zhou ◽  
Ivan GEORGE Fantus ◽  
Catharine Whiteside
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
High Glucose ◽  
Mesangial Cell ◽  
Cell Protein ◽  
Endothelin 1 ◽  
Kinase C ◽  
Protein Kinase C Isoforms

scholarly journals Effect of angiotensin-converting enzyme inhibition on protein kinase C and SR proteins in heart failure

1999 ◽  
Vol 276 (1) ◽  
pp. H53-H62 ◽  
Author(s):  
Yasuchika Takeishi ◽  
Ajit Bhagwat ◽  
Nancy A. Ball ◽  
Darryl L. Kirkpatrick ◽  
Muthu Periasamy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Angiotensin Converting Enzyme ◽  
Protein Expression ◽  
Guinea Pigs ◽  
Pressure Overload ◽  
Ace Inhibition ◽  
Converting Enzyme ◽  
Kinase C

We tested the hypothesis that activation of protein kinase C (PKC) isoforms in pressure-overload heart failure was prevented by angiotensin-converting enzyme (ACE) inhibition, resulting in normalization of cardiac sarcoplasmic reticulum (SR) Ca2+ATPase (SERCA) 2a and phospholamban protein levels and improvement in intracellular Ca2+ handling. Aortic-banded and control guinea pigs were given ramipril (5 mg ⋅ kg−1 ⋅ day−1) or placebo for 8 wk. Ramipril-treated banded animals had lower left ventricular (LV) and lung weight, improved survival, increased isovolumic LV mechanics, and improved cardiomyocyte Ca2+ transients compared with placebo-treated banded animals. This was associated with maintenance of SERCA2a and phospholamban protein expression. Translocation of PKC-α and -ε was increased in placebo-treated banded guinea pigs compared with controls and was attenuated significantly by treatment with ramipril. We conclude that ACE inhibition attenuates PKC translocation and prevents downregulation of Ca2+ cycling protein expression in pressure-overload hypertrophy. This represents a mechanism for the beneficial effects of this therapy on LV function and survival in heart failure.

Transcriptional Mechanism of Protein Kinase C-Induced Isoform-Specific Expression of the Gene for Endothelin-Converting Enzyme-1in Human Endothelial Cells

2001 ◽  
Vol 60 (6) ◽  
pp. 1332-1342 ◽  
Author(s):  
Hans-Dieter Orzechowski ◽  
Astrid Günther ◽  
Stefan Menzel ◽  
Andreas Zimmermann ◽  
Heiko Funke-Kaiser ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Converting Enzyme ◽  
Human Endothelial Cells ◽  
Specific Expression ◽  
Kinase C ◽  
Endothelin Converting Enzyme

scholarly journals High Glucose-suppressed Endothelin-1 Ca2+ Signaling via NADPH Oxidase and Diacylglycerol-sensitive Protein Kinase C Isozymes in Mesangial Cells

2003 ◽  
Vol 278 (36) ◽  
pp. 33951-33962 ◽  
Author(s):  
Hong Hua ◽  
Snezana Munk ◽  
Howard Goldberg ◽  
I. George Fantus ◽  
Catharine I. Whiteside
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nadph Oxidase ◽  
High Glucose ◽  
Mesangial Cells ◽  
Endothelin 1 ◽  
Kinase C

scholarly journals Dysregulation of protein kinase C in adult depression and suicide: evidence from postmortem brain studies

2021 ◽  
Author(s):  
Ghanshyam N Pandey ◽  
Anuradha Sharma ◽  
Hooriyah S Rizavi ◽  
Xinguo Ren
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Mrna Expression ◽  
Postmortem Brain ◽  
Cortical Region ◽  
Cytosol Fraction ◽  
Kinase C ◽  
Pkc Isozymes

Abstract Background Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study we examined the role of PKC isozymes in depression and suicide. Methods We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region [Brodmann area 9 (BA9)] in 24 normal control (NC) subjects, 24 depressed suicide (DS) subjects and 12 depressed non-suicide (DNS) subjects. The levels of mRNA in the prefrontal cortex (PFC) were determined by qRT-PCR and the protein expression was determined by Western blotting. Results We observed a significant decrease in mRNA expression of PKCα, PKCβI, PKCδ and PKCε and decreased protein expression either in the membrane or the cytosol fraction of PKC isozymes - PKCα, PKCβI, PKCβII and PKCδ in DS and DNS subjects compared with NC subjects. Conclusions The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.

scholarly journals N-Acetylcysteine and α-cyano-4-hydroxycinnamic acid alter protein kinase C (PKC)-δ and PKC-ζ and diminish dysmorphogenesis in rat embryos cultured with high glucose in vitro

2007 ◽  
Vol 192 (1) ◽  
pp. 207-214 ◽  
Author(s):  
Mattias Gäreskog ◽  
Parri Wentzel
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
High Glucose ◽  
Culture Medium ◽  
Hydroxycinnamic Acid ◽  
Oxygen Species ◽  
Rat Embryos ◽  
Protein Kinase C Inhibitors ◽  
Kinase C

Malformations and growth disturbances are two- to threefold more common in infants of diabetic mothers than in offspring of non-diabetic pregnancy. Several suggestions have emerged to explain the reasons for diabetic embryopathy, including enhanced mitochondrial production of reactive oxygen species leading to altered activation of protein kinase C. This study aimed to evaluate the effect of α-cyano-4-hydroxycinnamic acid (CHC) and N-acetylcysteine (NAC) addition on morphology and activity of protein kinase C-δ and protein kinase C-ζ in rat embryos exposed to a high glucose concentration in vitro. Day 9 embryos from normal rats were cultured in 10 or 30 mM glucose concentrations with or without supplementation of CHC, NAC, or protein kinase C inhibitors specific for protein kinase C-δ and protein kinase C-ζ. Embryos were evaluated for malformations, crown rump length, and somite number. Protein kinase C-δ and protein kinase C-ζ activities were estimated by western blot by separating membranous and cytosolic fractions of the embryo. We found increased malformations and growth retardation in embryos cultured in high versus low glucose concentrations. These abnormalities were diminished when CHC and NAC or specific protein kinase C-inhibitors were added to the culture medium. The activities of embryonic protein kinase C-δ and protein kinase C-ζ were increased in the high glucose environment after 24-h culture, but were normalized by the addition of CHC and NAC as well as respective inhibitor to the culture medium. These findings suggest that mitochondrial overproduction of reactive oxygen species is involved in diabetic embryopathy. Furthermore, such overproduction may affect embryonic development, at least partly, by enhancing the activities of protein kinase C-δ and protein kinase C-ζ.

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