Preptin, a 34-amino acid peptide derived from pro-IGF2, is believed to influence various physiological processes, including insulin secretion and the regulation of bone metabolism. Despite its recognized involvement, the precise physiological role of preptin remains enigmatic. To address this knowledge gap, we synthesized 16 analogs of preptin, spanning a spectrum from full-length forms to fragments, and conducted comprehensive comparative activity evaluations alongside native human, mouse and rat preptin. Our study aimed to elucidate the physiological role of preptin. Contrary to previous indications of broad biological activity, our thorough analyses across diverse cell types revealed no significant biological activity associated with preptin or its analogs. This suggests that the associations of preptin with various diseases or tissue-specific abundance fluctuations may be influenced by factors beyond preptin itself, such as higher levels of IGF2 or IGF2 proforms present in tissues. In conclusion, our findings challenge the conventional notion of preptin as an isolated biologically active molecule and underscore the complexity of its interactions within biological systems. Rather than acting independently, the observed effects of preptin may arise from experimental conditions, elevated preptin concentrations, or interactions with related molecules such as IGF2.
- MeSH
- insulinu podobný růstový faktor II * metabolismus MeSH
- inzulin metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- peptidové fragmenty metabolismus MeSH
- proteinové prekurzory metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Yohimbine, a natural indole alkaloid and a nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders and sepsis. Nevertheless, its broader clinical use faces challenges due to its low receptor selectivity. A structure-activity relationship study of novel yohimbine analogues identified amino esters of yohimbic acid as potent and selective ADRA2A antagonists. Specifically, amino ester 4n, in comparison to yohimbine, showed a 6-fold higher ADRA1A/ADRA2A selectivity index (SI > 556 for 4n) and a 25-fold higher ADRA2B/ADRA2A selectivity index. Compound 4n also demonstrated high plasma and microsomal stability, moderate-to-low membrane permeability determining its limited ability to cross the blood-brain barrier, and negligible toxicity on nontumor normal human dermal fibroblasts. Compound 4n represents an important complementary pharmacological tool to study the involvement of adrenoceptor subtypes in pathophysiologic conditions such as inflammation and sepsis and a novel candidate for further preclinical development to treat ADRA2A-mediated pathologies.
- MeSH
- alfa-2-adrenergní receptory - antagonisté * farmakologie chemie chemická syntéza MeSH
- alfa-2-adrenergní receptory * metabolismus MeSH
- lidé MeSH
- racionální návrh léčiv * MeSH
- vztahy mezi strukturou a aktivitou MeSH
- yohimbin * farmakologie chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
meso-Methyl BODIPY photocages stand out for their absorption properties and easy chromophore derivatization. However, their low uncaging efficiencies often hinder applications requiring release of protected substrates in high amounts. In this study, we demonstrate that the sulfonothioated BODIPY group photocleaves a sulfonylthio group from the meso-methyl position with a 10-fold higher quantum yield than the most efficient leaving groups studied to date. Photocleavage, observed in solution and in cells, is accompanied by the spatiotemporally controlled photorelease of H2Sn. For this reason, sulfonothioated BODIPY may be applied in cell signaling, redox homeostasis, and metabolic regulation studies.
- MeSH
- signální transdukce * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The reported method allows for a simple and rapid monitoring of DNA replication and cell cycle progression in eukaryotic cells in vitro. The DNA of replicating cells is labeled by incorporation of a metabolically-active fluorescent (Cy3) deoxyuridine triphosphate derivative, which is delivered into the cells by a synthetic transporter (SNTT1). The cells are then fixed, stained with DAPI and analyzed by flow cytometry. Thus, this protocol obviates post-labeling steps, which are indispensable in currently used incorporation assays (BrdU, EdU). The applicability of the protocol is demonstrated in analyses of cell cycles of adherent (U-2 OS, HeLa S3, RAW 264.7, J774 A.1, Chem-1, U-87 MG) and suspension (CCRF-CEM, MOLT-4, THP-1, HL-60, JURKAT) cell cultures, including those affected by a DNA polymerase inhibitor (aphidicolin). Owing to a short incorporation time (5-60 min) and reduced number of steps, the protocol can be completed within 1-2 h with a minimal cell loss and with excellent reproducibility.
- MeSH
- barvení a značení metody MeSH
- bromodeoxyuridin aplikace a dávkování MeSH
- buněčný cyklus * MeSH
- DNA analýza MeSH
- fluorescenční barviva aplikace a dávkování MeSH
- HeLa buňky MeSH
- HL-60 buňky MeSH
- Jurkat buňky MeSH
- karbocyaniny aplikace a dávkování MeSH
- lidé MeSH
- průtoková cytometrie metody MeSH
- replikace DNA * MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
G-quadruplexes belong to noncanonical secondary structures of the nucleic acids commonly referred to as non-B DNA. In recent years there is growing evidence about the existence of G-quadruplex structures in vivo and their important regulatory roles in biological processes. This mini-review brings up the latest results on the transcriptional regulation by G-quadruplexes. On one hand G-quadruplexes might inhibit general expression potential of the genes as a part of a basal transcription activity, which is not specific to any genes or pathways. On the other hand, G-quadruplexes might dynamically monitor the activity of a gene together with other secondary structures localized predominantly in regulatory regions such as promoters, transcription start sites and transcription termination sites. Last but not least, it has been shown that G-quadruplexes serve as sensors of oxidative stress and subsequently modulate the transcription. The inhibitory or stimulatory effect of the G-quadruplexes on a gene transcription depends on its position on the template or coding strand.
Two molecules of mistaken identity are addressed. Uncovering these assignment errors led us to formulate more general guidelines about additional misassignments in cases of published bis-imines derived from 1,2-phenylenediamine and hydroxybenzaldehydes having no substituent in ortho-positions. The main purpose of this article is to highlight this repetitive assignment error in the literature and thus increase the likelihood of correct assignments in future papers.
- MeSH
- DNA chemie MeSH
- G-kvadruplexy * MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
- práce podpořená grantem MeSH
In this review, we analyze endocrine aspects of the relationships between antlerogenesis and rank-related behavior. The explanation of these relationships has been based on the presumption that the antler growth is regulated by hormones modulated by agonistic behavior. Originally, we assumed that these relationships are primarily testosterone dependent. In the eighties, it was reported that the insulin-like growth factor 1 (IGF-1) is the antler-stimulating hormone. This hypothesis was supposed to replace an earlier theory that the antler-stimulating hormones are either androgens or their derivatives. Here, we present historical and recent views on these issues. In particular, we analyze the arguments in favor and against the role of testosterone and IGF-1 in antler growth and present a comparison of the results obtained across some deer species. In this context, we review and discuss experiments with castration of various deer species and analyze data from papers dealing with in vivo studies. We conclude that testosterone and not IGF-1 is the main antler stimulating and regulating hormone, and that concentrations of testosterone may be modified by social behavior.
- MeSH
- chování zvířat MeSH
- endokrinní žlázy fyziologie MeSH
- parohy růst a vývoj MeSH
- vysoká zvěř růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Antlers as a potential model for bone growth and development have become an object of rising interest. To elucidate processes explaining how antler growth is regulated, in vitro cultures have been established. However, until now, there has been no standard method to cultivate antler cells and in vitro results are often opposite to those reported in vivo. In addition, many factors which are often not taken into account under in vitro conditions may play an important role in the development of antler cells. In this study we investigated the effects of the antler growth stage, the male individuality, passaged versus primary cultures and the effect of foetal calf serum concentrations on proliferative potential of mixed antler cell cultures in vitro, derived from regenerating antlers of red deer males (Cervus elaphus). The proliferation potential of antler cells was measured by incorporation of (3)H thymidine. Our results demonstrate that there is no significant effect of the antler growth stage, whereas male individuality and all other examined factors significantly affected antler cell proliferation. Furthermore, our results suggest that primary cultures may better represent in vivo conditions and processes occurring in regenerating antlers. In conclusion, before all main factors affecting antler cell proliferation in vitro will be satisfactorily investigated, results of in vitro studies focused on hormonal regulation of antler growth should be taken with extreme caution.
- MeSH
- kultivované buňky MeSH
- parohy cytologie MeSH
- proliferace buněk MeSH
- sérum MeSH
- vysoká zvěř anatomie a histologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
