The amyloid cascade hypothesis postulates that extracellular deposits of amyloid β (Aβ) are the primary and initial cause leading to the full development of Alzheimer's disease (AD) with intracellular neurofibrillary tangles; however, the details of this mechanism have not been fully described until now. Our preliminary data, coming from our day-to-day neuropathology practice, show that the primary location of the hyperphosphorylated tau protein is in the vicinity of the cell membrane of dystrophic neurites. This observation inspired us to formulate a hypothesis that presumes an interaction between low-density lipoprotein receptor-related protein 1 (LRP1) and fibrillar aggregates of, particularly, Aβ42 anchored at the periphery of neuritic plaques, making internalization of the LRP1-Aβ42 complex infeasible and, thus, causing membrane dysfunction, leading to the tauopathy characterized by intracellular accumulation and hyperphosphorylation of the tau protein. Understanding AD as a membrane dysfunction tauopathy may draw attention to new treatment approaches not only targeting Aβ42 production but also, perhaps paradoxically, preventing the formation of LRP1-Aβ42.
- MeSH
- Alzheimerova nemoc * metabolismus patologie etiologie MeSH
- amyloidní beta-protein * metabolismus MeSH
- buněčná membrána metabolismus MeSH
- fosforylace MeSH
- lidé MeSH
- peptidové fragmenty metabolismus MeSH
- protein 1 související s LDL-receptory * metabolismus MeSH
- proteiny tau * metabolismus MeSH
- tauopatie * metabolismus patologie etiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND/AIM: Follicle-stimulating hormone receptor (FSHr), expressed on endothelial cells of vessels in different malignant tumors, has been recently investigated as a potential pan-receptor of cancer treatment. However, the expression of this receptor has also been confirmed in other tissues under pathological conditions including cancer. The aim of the presented pilot study was to evaluate the expression of FSHr in head and neck squamous cancer (HNSCC). PATIENTS AND METHODS: A total of 28 HNSCC patient samples were immunohistochemically analyzed for the presence of FSHr using a commercially available primary antibody. RESULTS: FSHr was detected not only in the tumor tissue, but also in the basal layer or dysplastic parts of squamous mucosa and also in fibroblasts surrounding the tumor tissue. CONCLUSION: FSHr is present on different benign or malignant mesenchymal and epithelial structures in HNSCC. A brief literature review revealed a wider role of FSHr in the development of neoplasia.
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku metabolismus MeSH
- imunohistochemie MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- pilotní projekty MeSH
- receptory FSH metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Oligomer aggregation of green-to-red photoconvertible fluorescent protein Eos (EosFP) is a natural feature of the wild‑type variant. The aim of the present study was to follow up mitochondrial nucleoid behavior under natural conditions of living cells transfected with mitochondrial single‑strand DNA‑binding protein (mtSSB) conjugated with EosFP. HEPG2 and SH‑SY5Y cells were subjected to lentiviral transfection and subsequently immunostained with anti‑DNA, anti‑transcription factor A, mitochondrial (TFAM) or anti‑translocase of the inner membrane 23 antibodies. Fluorescent microscopy, conventional confocal microscopy, superresolution biplane fluorescence photo-activation localization microscopy and direct stochastic optical reconstruction microscopy were used for imaging. In the two cell types, apparent couples of equally‑sized mtSSB‑EosFP‑visualized dots were observed. During the time course of the ongoing transfection procedure, however, a small limited number of large aggregates of mtSSB‑EosFP‑tagged protein started to form in the cells, which exhibited a great co‑localization with the noted coupled positions. Antibody staining and 3D immunocytochemistry confirmed that nucleoid components such as TFAM and DNA were co‑localized with these aggregates. Furthermore, the observed reduction of the mtDNA copy number in mtSSB‑EosFP‑transfected cells suggested a possible impairment of nucleoid function. In conclusion, the present study demonstrated that coupled nucleoids are synchronized by mtSSB‑EosFP overexpression and visualized through their equal binding capacity to mtSSB‑EosFP‑tagged protein. This observation suggested parallel replication and transcription activity of nucleoid couples native from a parental one. Preserved coupling in late stages of artificial EosFP‑mediated aggregation of tagged proteins suggested a rational manner of mitochondrial branching that may be cell-type specifically dependent on hierarchical nucleoid replication.
- MeSH
- DNA vazebné proteiny chemie metabolismus MeSH
- genetická transkripce MeSH
- genová dávka MeSH
- imunohistochemie MeSH
- konfokální mikroskopie MeSH
- lidé MeSH
- mitochondriální DNA metabolismus MeSH
- mitochondriální proteiny metabolismus MeSH
- mitochondrie metabolismus MeSH
- multimerizace proteinu * MeSH
- nádorové buněčné linie MeSH
- rekombinantní fúzní proteiny chemie metabolismus MeSH
- transkripční faktory metabolismus MeSH
- transport proteinů MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIM: We investigated differences of metastatic spread of normal proteinase-activated receptor-2 (Par2+/+) melanoma B16 in Par2-/- (knock-out) animals compared to C57Bl6 mice. MATERIALS AND METHODS: Nine knock-out mice B6.Cg-F2rl1tm1Mslb/J (Par2-/-) and nine C57Bl6/J controls were subcutaneously inoculated with B16 melanoma tissue cells. Twelve days after inoculation, all primary tumors were removed. Survival and metastatic spread was followed for up to 100 days after primary tumor extirpation. RESULTS: Excised primary tumors were on average larger in Par2-/- mice (360 mm3 vs. 221 mm3 in C57Bl6/J). Distant spontaneous metastases developed in only 3 of 9 of Par2-/- mice in comparison to 6 of 9 controls. The average survival time was 84 days in Par2-/- animals compared to 63 days in C57Bl6/J mice. CONCLUSION: Host Par2 melanoma model contributes to the limitation of local cancer progression in one area, while on the other hand is important for enhancing distant metastatic spread.
- MeSH
- imunohistochemie MeSH
- melanom experimentální genetika metabolismus patologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- receptor PAR-2 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- WOBENZYM, PHLOGENZYM,
- MeSH
- antiflogistika nesteroidní aplikace a dávkování terapeutické užití MeSH
- enzymoterapie MeSH
- enzymy aplikace a dávkování farmakologie MeSH
- hydrolasy aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- placebo MeSH
- sportovní úrazy dějiny farmakoterapie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- botulismus etiologie MeSH
- botulotoxiny metabolismus škodlivé účinky MeSH
- Clostridium botulinum MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- PHLOGENZYM,
- MeSH
- aplikace orální MeSH
- intestinální absorpce MeSH
- lidé MeSH
- proteasy metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- WOBENZYM, PHLOGENZYM,
- MeSH
- cytokiny MeSH
- endopeptidasy fyziologie MeSH
- enzymoterapie MeSH
- enzymy fyziologie MeSH
- krevní oběh MeSH
- lidé MeSH
- lipoproteiny LDL krev MeSH
- molekuly buněčné adheze MeSH
- trypsin MeSH
- Check Tag
- lidé MeSH
