101 research outputs found
Purification and Characterization of Two Casein Kinase Type II Isozymes from Bovine Brain Gray Matter
No full textIdentification of HB-EGF - Rac1 - c-Myc signalling pathway in growing human keratinocytes
No full textThe functions of the autocrine growth factor Heparin Binding-Epidermal Growth Factor (HB-EGF), the Rho guanosine triphosphatase Rac1 and the transcription factor c-Myc have been extensively studied in epidermal keratinocytes. Each of the three proteins has been found to mediate both pro proliferative and pro migratory effects and to accelerate the process of wound healing. Despite the established functions of HB-EGF, Rac1 and c-Myc appear to complement one another, the possible functional connection between the three proteins has never been examined. Herewith we are the first to establish the existence of a functional link between HB-EGF, Rac1 and c-Myc. We have found that siRNA-mediated Rac1 knock down in growing human keratinocytes causes accumulation of the endogenous HB-EGF protein and inhibits c-Myc- Ser62/Thr58 phosphorylation. We have observed for the first time that the treatment with exogenous HB-EGF induces Ser62/Thr58 phosphorylation of c-Myc and this effect is then mediated by Rac1. Our results suggest the existence of HB-EGF-Rac1-c-Myc axis in human keratinocytes proliferation and migration.</p
8-isorpostanes – markers for oxidative stress in obstructive sleep apnea patients with systolic dysfunction
No full textRadostina Vlaeva Cherneva,1 Ognian Borisov Georgiev,1 Daniela Stoichkova Petrova,1 Emil Ivanov Manov,2 Sylvia Rumenova Ruseva,3 Vanio Ivanov Mitev,3 Julia Ivanova Petrova4 1Department of Internal Medicine, Division of Pulmonary Medicine, Medical University of Sofia, Sofia, Bulgaria; 2Department of Internal Medicine, Division of Cardiology, Medical University of Sofia, Sofia, Bulgaria; 3Department of Medical Chemistry and Biochemistry, Laboratory of Synthesis and Analysis of Bioactive Substances, Medical University of Sofia, Sofia, Bulgaria; 4Department of Neurology, Medical University of Sofia, Sofia, Bulgaria Objective: Increased oxidative stress is considered to be an independent risk factor for cardiovascular diseases, but remains disputed in obstructive sleep apnea (OSA). Among oxidative stress markers, isorpostanes are considered to be the most sensitive and specific. Aims: The aim of the study was to compare urinary isorpostanes in patients with OSA and systolic dysfunction to patients with OSA and preserved ejection fraction (EF) and determine their role as markers for increased oxidative stress and early cardiac damage. Materials and methods: Urinary 8F2-isorpostanes were measured in 30 patients with OSA and mild systolic dysfunction (EF = 45.7% ± 6.17%) and compared to 15 patients with OSA and normal EF (EF = 60.3% ± 6.3%). Univariate regression analysis was performed to find predictors of left systolic dysfunction. Correlations between 8-isorpostanes, anthropometric, metabolic, and sleep study characteristics were explored. In addition, in 19 patients the effect of bilevel positive airway pressure (BiPAP) therapy was evaluated during a 3 month follow-up. Markers of hemodynamic stress, N-terminal prohormone of brain natriuretic peptide and oxidative stress, measured by 8-isorpostanes were compared before and after the follow-up. Results: Urinary levels of 8-isorpostanes were significantly higher in the group with mild systolic dysfunction in comparison to the controls with preserved EF (0.149 versus 0.049 pg/µL, P = 0.023). The regression analysis did not define them as predictors for left systolic dysfunction. Their urinary concentration correlated best to the average desaturation index (P = 0.043). Urinary 8-isorpostanes decreased as a result of BiPAP therapy after three months of follow-up (0.164 versus 0.098 pg/µL, P = 0.011). Conclusion: Urinary isorpostanes are reliable markers for chronic intermittent hypoxia and oxidative stress in OSA patients. They may be of clinical application for the early detection of patients at risk for cardiovascular damage and could help in the monitoring of the restoration of oxidative balance. Keywords: 8-isorpostanes, oxidative stress, LV systolic dysfunction, OS
Genetic and Epidemiological Indications for Adiponectin Gene Dysregulation in Gestational Diabetes Mellitus
No full textEffects of the Cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) on the physiology of cultured human keratinocytes
No full textCYC202 (R-roscovitine) is a potent cyclin-dependent kinase inhibitor, investigated as a potential anti-cancer agent. The knowledge of the action of this pharmacological agent on normal human cells is still limited. In this study, we have explored the effects of the cyclin-dependent kinase inhibitor CYC202 on normal human epidermal keratinocytes. The loss of cell viability induced by this compound was strongly dependent on the rate of keratinocyte proliferation. At slightly cytotoxic doses, CYC202 inhibited the proliferation of subconfluent keratinocytes in a dose-dependent manner, and at higher concentrations induction of early apoptosis was observed, evidenced by caspase-3 activation. The signal transduction pathways in subconfluent keratinocytes were altered, as CYC202 increased the phosphorylation of p38 MAP kinase. The activation of this kinase was confirmed by the increased phosphorylation of p38 MAPK substrate, the small heat shock protein HSP27. Prolonged inhibition of highly proliferative cells with CYC202 for 48 and 72 h altered the expression of epidermal differentiation markers. The use of the selective p38 kinase inhibitor PD169316 demonstrated that involucrin mRNA was upregulated by CYC202 via p38 MAPK pathway. These effects were strongly dependent on cell density and were observed only in highly proliferative keratinocytes. We concluded that CYC202 although highly potent against cancer cells inhibits also the proliferation and induces early apoptotic events in autocrine culture of normal human keratinocytes, activates p38 MAP kinase pathway and alters the expression of the epidermal differentiation markers. These results suggest that despite this potency against tumour cells, CYC202 must be used attentively in the clinical practice.</p
-induced p44/p42 mitogen-activated protein kinase activation in murine fibroblasts and attenuates in vitro infection
No full textProtein kinase C-independent activation of mitogen-activated protein kinase by epidermal growth factor in skin fibroblasts
No full textInsight into the Metabolite Pattern of Psoriasis: Correlation among Homocysteine, Methionine, and Polyamines
No full textPsoriasis is an incurable dermatological disorder, characterized by increased epidermal cell proliferation. Numerous studies have focused on the modulation of polyamine (PA) metabolism in psoriatic lesions, as well as the relationship between serum homocysteine (Hcy) levels and psoriasis severity. The correlation between Hcy and PA levels has not been investigated, although both of them depend on methionine (Met) loading. The aim of this study was to examine Met, Hcy, and polyamine levels in serum, saliva, lesions, and non-affected skin to investigate the eventual relationship between their levels in skin samples and to assess the correlation of each metabolite among the tested samples. This study was conducted on 24 patients with plaque-form psoriasis vulgaris. The original LC-MS/MS method was used for quantification of analytes. Hyperhomocysteinemia was observed and the serum levels of spermidine (Spd) and spermine (Spm) were also found to be elevated. A significant increase in Met (p < 0.05) and Spm (p < 0.001) concentrations in the psoriatic plaques were found, when compared to the non-affected skin. Significant correlations were established between all polyamines levels and between methionine and spermine in both types of cutaneous samples. This study illustrates the tight relationship between Met and Polyamine levels in epidermis of psoriatic patients. Our results could be helpful in psoriasis treatment, highlighting the importance of the balanced protein diet and intake of vitamins B12 and B9
Effect of chemical blocade of different signal transduction pathways on map kinase tyrosine phosphorylation in rabbit mammary cells
No full textInternational audienc
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