Cardiovascular side effects are frequent problems accompanying systemic glucocorticoid therapy, although the underlying mechanisms are not fully resolved. Reactive oxygen species (ROS) have been shown to promote various cardiovascular diseases although the link between glucocorticoid and ROS signaling has been controversial. As the family of NADPH oxidases has been identified as important source of ROS in the cardiovascular system we investigated the role of NADPH oxidases in response to the synthetic glucocorticoid dexamethasone in the cardiovascular system in vitro and in vivo in mice lacking functional NADPH oxidases due to a mutation in the gene coding for the essential NADPH oxidase subunit p22phox. We show that dexamethasone induced NADPH oxidase-dependent ROS generation, leading to vascular proliferation and angiogenesis due to activation of the transcription factor hypoxia-inducible factor-1 (HIF1). Chronic treatment of mice with low doses of dexamethasone resulted in the development of systemic hypertension, cardiac hypertrophy and left ventricular dysfunction, as well as in pulmonary hypertension and pulmonary vascular remodeling. In contrast, mice deficient in p22phox-dependent NADPH oxidases were protected against these cardiovascular side effects. Mechanistically, dexamethasone failed to upregulate HIF1α levels in these mice, while vascular HIF1α deficiency prevented pulmonary vascular remodeling. Thus, p22phox-dependent NADPH oxidases and activation of the HIF pathway are critical elements in dexamethasone-induced cardiovascular pathologies and might provide interesting targets to limit cardiovascular side effects in patients on chronic glucocorticoid therapy.

• MeSH
• faktor 1 indukovatelný hypoxií MeSH
• glukokortikoidy MeSH
• lidé MeSH
• myši MeSH
• NADPH-oxidasy genetika   MeSH
• nemoci srdce * MeSH
• plicní hypertenze * chemicky indukované   MeSH
• reaktivní formy kyslíku MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The effect of crop rotation and monocropping on the occurrence of bacteria with antagonistic activity toward Pythium debaryanum and Fusarium oxysporum was shown. Arthrobacter spp., fluorescent Pseudomonas spp. and actinomycetes were isolated from winter rape, sugar beet and winter barley rhizosphere and bulk soil from the plots of a long-term crop rotation experiment (18 years). The occurrence of mycoantagonistic isolates and their antibiosis level exhibited specificity for the site, crop and crop rotation. Mycoantagonistic activity was common among actinomycetes and fluorescent Pseudomonas spp. and less frequent among Arthrobacter spp. Antibiosis of fluorescent Pseudomonas spp. and Arthrobacter spp. was in general stronger against P. debaryanum than F. oxysporum. The highest percentage of antagonistic Pseudomonas spp. against P. debaryanum was in the plots of barley crop, while plots of winter rape showed higher frequency of antagonists against F. oxysporum. The highest antibiosis activity of Arthrobacter spp. against both pathogens occurred in isolates from barley and winter rape monoculture, and there were no F. oxysporum antagonists among these bacteria in sugar beet monoculture. Most of actinomycete isolates strongly inhibited growth of P. debaryanum and F. oxysporum. The percentage of mycoantagonistic actinomycetes and their antibiosis level were the highest in the 6-year crop rotation system.

• MeSH
• antibióza MeSH
• Bacteria izolace a purifikace   MeSH
• Fusarium fyziologie   MeSH
• fyziologie bakterií MeSH
• nemoci rostlin mikrobiologie   MeSH
• půdní mikrobiologie MeSH
• Pythium fyziologie   MeSH
• zemědělské plodiny mikrobiologie   růst a vývoj   MeSH
• zemědělství metody   MeSH
• Publikační typ
• hodnotící studie MeSH

The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the Hif1a gene encoding the transcription factor hypoxia-inducible factor 1α (HIF-1α) is mediated by an Islet1-Cre transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These Hif1aCKO mice demonstrate significantly decreased perinatal survival and impaired left ventricular function. The absence of HIF-1α impaired the survival and proliferation of preganglionic and postganglionic neurons of the sympathetic system, respectively. These defects resulted in hypoplasia of the sympathetic ganglion chain and decreased sympathetic innervation of the Hif1aCKO heart, which was associated with decreased cardiac contractility. The number of chromaffin cells in the adrenal medulla was also decreased, indicating a broad dependence on HIF-1α for development of the sympathetic nervous system.

• MeSH
• anomálie koronárních cév embryologie   MeSH
• chromafinní buňky MeSH
• dřeň nadledvin embryologie   inervace   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa fyziologie   MeSH
• koronární cévy embryologie   MeSH
• myši knockoutované MeSH
• myši transgenní MeSH
• myši MeSH
• srdce embryologie   inervace   MeSH
• sympatická ganglia embryologie   růst a vývoj   MeSH
• sympatický nervový systém enzymologie   růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

• MeSH
• Evropská unie MeSH
• lidé MeSH
• mezinárodní spolupráce * MeSH
• molekulární biologie organizace a řízení   trendy   MeSH
• oxidace-redukce MeSH
• reaktivní formy kyslíku chemie   metabolismus   MeSH
• signální transdukce MeSH
• společnosti vědecké MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH