High glucose-induced growth factor resistance in human fibroblasts can be reversed by antioxidants and protein kinase C-inhibitors

1997 ◽  
Vol 15 (3) ◽  
pp. 197-201 ◽  
Author(s):  
Karin Hehenberger ◽  
Anders Hansson
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
High Glucose ◽  
Human Fibroblasts ◽  
Protein Kinase C Inhibitors ◽  
Kinase C

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.

scholarly journals Stimulation of hyaluronan biosynthesis by platelet-derived growth factor-BB and transforming growth factor-β1 involves activation of protein kinase C

1995 ◽  
Vol 307 (3) ◽  
pp. 817-821 ◽  
Author(s):  
M Suzuki ◽  
T Asplund ◽  
H Yamashita ◽  
C H Heldin ◽  
P Heldin
Keyword(s):  
Protein Kinase C ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Transforming Growth Factor Β1 ◽  
Platelet Derived Growth Factor ◽  
Tgf Beta ◽  
Kinase C

The intracellular signal transduction pathways that mediate the stimulatory effects of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-beta on hyaluronan biosynthesis in human fibroblasts were investigated. The stimulatory effects of both PDGF-BB and TGF-beta 1 were dependent on protein kinase C (PKC), since the PKC inhibitor calphostin C inhibited the stimulation by the growth factors. Direct activation of PKC by phorbol 12-myristate 13-acetate (PMA) also stimulated hyaluronan production, and the combination of either PDGF-BB or TGF-beta 1 and PMA gave an increased effect. One possible mechanism for activation of PKC is via induction of phospholipase C (PLC) activity; U-17322, an inhibitor of PLC-gamma, was found to inhibit partially PDGF-BB-stimulated hyaluronan synthesis. PDGF-BB is known to activate PLC-gamma through tyrosine phosphorylation; however, a PDGF beta-receptor mutant unable to interact with and activate PLC-gamma was still able to mediate induction of hyaluronan biosynthesis, indicating that PDGF-mediated stimulation is not entirely dependent on PLC-gamma. The stimulations by PDGF-BB and TGF-beta 1 were partly dependent on protein synthesis, since parts of the effects were inhibited by cycloheximide; in contrast, the effects mediated by PMA were not. Our results indicate that PKC is involved in the transduction of the effects of growth factors on hyaluronan biosynthesis, and that the effects involve direct or indirect activation of existing hyaluronan synthetase molecules, as well as induction of new enzyme molecules.

scholarly journals Protein Kinase C Inhibitors Attenuate Protective Effect of High Glucose against Hypoxic Injury in H9c2 Cardiac Cells.

2000 ◽  
Vol 50 (6) ◽  
pp. 645-649 ◽  
Author(s):  
Chang-Hyun Moon ◽  
Yi-Sook Jung ◽  
Min Hwa Kim ◽  
Rhan Mi Park ◽  
Soo Hwan Lee ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protective Effect ◽  
High Glucose ◽  
Cardiac Cells ◽  
Hypoxic Injury ◽  
Protein Kinase C Inhibitors ◽  
Kinase C
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