To assess the potential role of IL-6 in sciatic nerve injury-induced activation of a pro-regenerative state in remote dorsal root ganglia (DRG) neurons, we compared protein levels of SCG-10 and activated STAT3, as well as axon regeneration in IL-6 knockout (IL-6ko) mice and their wild-type (WT) counterparts. Unilateral sciatic nerve compression and transection upregulated SCG-10 protein levels and activated STAT3 in DRG neurons not only in lumbar but also in cervical segments of WT mice. A pro-regenerative state induced by prior sciatic nerve lesion in cervical DRG neurons of WT mice was also shown by testing for axon regeneration in crushed ulnar nerve. DRG neurons from IL-6ko mice also displayed bilaterally increased levels of SCG-10 and STAT3 in both lumbar and cervical segments after sciatic nerve lesions. However, levels of SCG-10 protein in lumbar and cervical DRG of IL-6ko mice were significantly lower than those of their WT counterparts. Sciatic nerve injury induced a lower level of SCG-10 in cervical DRG of IL-6ko than WT mice, and this correlates with significantly shorter regeneration of axons distal to the crushed ulnar nerve. These results suggest that IL-6 contributes, at the very least, to initiation of the neuronal regeneration program in remote DRG neurons after unilateral sciatic nerve injury.
- MeSH
- imunohistochemie MeSH
- interleukin-6 analýza nedostatek metabolismus MeSH
- intracelulární signální peptidy a proteiny analýza MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- neurony chemie cytologie metabolismus patologie MeSH
- poranění periferního nervu metabolismus patologie chirurgie MeSH
- regenerace nervu * MeSH
- spinální ganglia cytologie metabolismus patologie chirurgie MeSH
- transkripční faktor STAT3 analýza MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We studied the effect of ellagic acid (EA) on the morphology of nucleoli and on the pattern of major proteins of the nucleolus. After EA treatment of HeLa cells, we observed condensation of nucleoli as documented by the pattern of argyrophilic nucleolar organizer regions (AgNORs). EA also induced condensation of RPA194-positive nucleolar regions, but no morphological changes were observed in nucleolar compartments positive for UBF1/2 proteins or fibrillarin. Studied morphological changes induced by EA were compared with the morphology of control, non-treated cells and with pronounced condensation of all nucleolar domains caused by actinomycin D (ACT-D) treatment. Similarly as ACT-D, but in a lesser extent, EA induced an increased number of 53BP1-positive DNA lesions. However, the main marker of DNA lesions, γH2AX, was not accumulated in body-like nuclear structures. An increased level of γH2AX was found by immunofluorescence and Western blots only after EA treatment. Intriguingly, the levels of fibrillarin, UBF1/2 and γH2AX were increased at the promoters of ribosomal genes, while 53BP1 and CARM1 levels were decreased by EA treatment at these genomic regions. In the entire genome, EA reduced H3R17 dimethylation. Taken together, ellagic acid is capable of significantly changing the nucleolar morphology and protein levels inside the nucleolus.
- MeSH
- buněčné dělení účinky léků MeSH
- buněčné jadérko chemie účinky léků ultrastruktura MeSH
- chromozomální proteiny, nehistonové analýza MeSH
- daktinomycin farmakologie MeSH
- epigeneze genetická účinky léků MeSH
- G2 fáze účinky léků MeSH
- guanylátcyklasa analýza antagonisté a inhibitory MeSH
- HeLa buňky chemie účinky léků MeSH
- histony analýza metabolismus MeSH
- intracelulární signální peptidy a proteiny analýza MeSH
- kyselina ellagová farmakologie MeSH
- lidé MeSH
- metylace MeSH
- nádorové proteiny analýza MeSH
- organizátor jadérka chemie účinky léků ultrastruktura MeSH
- poškození DNA MeSH
- posttranslační úpravy proteinů účinky léků MeSH
- promotorové oblasti (genetika) MeSH
- ribozomální DNA účinky léků genetika MeSH
- RNA-polymerasa I analýza MeSH
- signální adaptorové proteiny CARD analýza antagonisté a inhibitory MeSH
- transkripční iniciační komplex Pol1 - proteiny analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Dkk-1 in human serum has a high predictive value as a potential marker (specificity 100 %, positive predictive value 100 %) in laboratory diagnosis of osteoporosis.
AIM: Endoglin is a homodimeric transmembrane glycoprotein that has been demonstrated to affect transforming growth factor beta (TGF-beta) signaling and endothelial nitric oxide synthase (eNOS) expression by affecting SMAD proteins in vitro. Thus, in this study we stepped forward to elucidate whether endoglin is co-expressed with SMAD2, phosphorylated SMAD2/3 proteins and eNOS in vivo in atherosclerotic lesions in ApoE/LDLR double knockout mice. In addition, we sought whether endoglin expression as well as the expression of SMAD2, phosphorylated SMAD2/3 and eNOS is affected by atorvastatin treatment. METHODS: Two-month-old female ApoE/LDLR double knockout mice were divided into two groups. The control group was fed with the western type diet whereas in the atorvastatin group, atorvastatin at dose 100 mg/kg per day was added to the same diet. Immunohistochemical and western blot analysis of endoglin, SMAD2, phosphorylated SMAD2/3 and eNOS expressions in aorta were performed. RESULTS: The biochemical analysis showed that administration of atorvastatin significantly decreased level of total cholesterol, VLDL, LDL, TAG, and significantly increased level of HDL cholesterol. Fluorescence immunohistochemistry showed endoglin co-expression with SMAD2, phosphorylated SMAD2/3 and eNOS in aortic endothelium covering atherosclerotic lesions in both control and atorvastatin treated mice. Western blot analysis demonstrated that atorvastatin significantly increased expression of endoglin, SMAD2, phosphorylated SMAD2/3, and eNOS in mice aorta. CONCLUSION: These findings suggest, that endoglin might be interesting marker of endothelial dysfunction and/or atherogenesis which is upregulated by statins implicating potential beneficial role of endoglin and its pathway in atherosclerosis.
- MeSH
- anticholesteremika farmakologie MeSH
- aorta chemie MeSH
- apolipoproteiny E genetika MeSH
- ateroskleróza metabolismus MeSH
- cévní endotel chemie MeSH
- fosforylace MeSH
- imunohistochemie MeSH
- intracelulární signální peptidy a proteiny analýza MeSH
- kyseliny heptylové farmakologie MeSH
- myši knockoutované MeSH
- myši MeSH
- protein Smad2 analýza MeSH
- protein Smad3 analýza MeSH
- pyrroly farmakologie MeSH
- receptory LDL genetika MeSH
- synthasa oxidu dusnatého, typ III analýza MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Endoglin (CD105) is a homodimeric transmembrane glycoprotein strongly related to transforming growth factor (TGF)-beta signaling and many pathological states. In this study, we wanted to evaluate whether endoglin is expressed in normocholesterolemic and hypercholesterolemic C57BL/6J mice as well as whether it is affected by atorvastatin treatment in these mice. C57BL/6J mice were fed with chow diet or an atherogenic diet for 12 weeks after weaning. In 2 atorvastatin-treated groups, mice were fed the same diets (chow or atherogenic) as described above except atorvastatin was added at the dosage of 10 mg x kg(-1) x day(-1) for the last 8 weeks before euthanasia. Biochemical analysis of blood samples revealed that administration of atherogenic diet significantly increased levels of total cholesterol, VLDL, LDL, and decreased levels of HDL. Atorvastatin treatment resulted in a significant decrease in total cholesterol and VLDL only in mice fed by atherogenic diet. Quantitative stereological analysis revealed that atorvastatin significantly decreased endothelial expression of endoglin in C57BL/6J mice fed the atherogenic diet. In conclusion, we demonstrated that endothelial expression of endoglin is upregulated by hypercholesterolemia and decreased by the hypolipidemic effect of atorvastatin in C57BL/6J mice, suggesting that endoglin expression could be involved in atherogenesis.
- MeSH
- antigeny CD31 analýza MeSH
- cévní endotel chemie MeSH
- financování organizované MeSH
- hypercholesterolemie farmakoterapie metabolismus MeSH
- imunohistochemie MeSH
- intracelulární signální peptidy a proteiny analýza MeSH
- kyseliny heptylové terapeutické užití MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- oxid dusnatý fyziologie MeSH
- pyrroly terapeutické užití MeSH
- statiny terapeutické užití MeSH
- transformující růstový faktor beta fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- MeSH
- cvičení fyziologie MeSH
- ektopické hormony metabolismus MeSH
- endokrinologie MeSH
- finanční podpora výzkumu jako téma MeSH
- interleukin-6 metabolismus MeSH
- intracelulární signální peptidy a proteiny analýza metabolismus MeSH
- leptin analýza metabolismus MeSH
- lidé MeSH
- metabolický syndrom etiologie metabolismus prevence a kontrola MeSH
- obezita etiologie MeSH
- tělesná námaha MeSH
- TNF-alfa metabolismus terapeutické užití MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
