19 research outputs found
Physiopathological Implications of 7TM Receptors
Seven-transmembrane (7TM) receptors are one of the most important proteins involved in perception of extracellular stimuli and regulation of variety of intracellular signaling pathways. Divergence of receptor types, their ligands and signaling pathways makes 7TM receptors important factors in pathology of many diseases. This review focused on the main diseases in which involvement of 7TM receptors was established e.g., retinitis pigmentosa, severe obesity, and dwarfism. Recent findings of aberrant expression of 7TM receptors in development of cancer were also summarized
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Physiopathological Implications of 7TM Receptors
Seven-transmembrane (7TM) receptors are one of the most important proteins involved in perception of extracellular stimuli and regulation of variety of intracellular signaling pathways. Divergence of receptor types, their ligands and signaling pathways makes 7TM receptors important factors in pathology of many diseases. This review focused on the main diseases in which involvement of 7TM receptors was established e.g., retinitis pigmentosa, severe obesity, and dwarfism. Recent findings of aberrant expression of 7TM receptors in development of cancer were also summarized
Involvement of G-protein Coupled Estrogen Receptor in physiology and physiopathology
Estrogens, without doubt, play a pivotal role in the regulation of both physiological and pathological processes. A plethora of intercellular signaling pathways are regulated by estrogens on both genomic, and non–genomic pathways via canonical ERα and ERβ receptors. Studies published in recent years showed that not all biological effects of estrogens can be attributed to the classical model of estrogen signaling. Aside canonical ERα and ERβ receptors a G–protein coupled estrogen receptor plays its role in estrogen mediated regulation of various tissues and organs. Ubiquitous presence of G–protein coupled estrogen receptor in different tissues, as well as observed de–regulation of its expression in multiple pathologies suggest an important role of this receptor in functioning of cells, tissues and organisms. Activation/deactivation of GPER estrogen receptor takes place during the metabolism of carbohydrates, lipids and immunological response, it is involved in a number of events from reproductive, cardiovascular, neurological and skeletal systems.Estrogeny, bez wątpienia, odgrywają istotną rolę w regulacji procesów fizjologicznych i patofizjologicznych. Za pośrednictwem kanonicznych recepto– rów estrogenów ERα i ERβ hormony te modulują wiele ścieżek sygnałowych w komórce zarówno na drodze genomowej, jak i niegenomowej. Wyniki badań ostatnich lat ujawniają, że nie wszystkie biologiczne efekty estrogenów wynikają z ich klasycznego modelu działania. Obok kanonicznych receptorów ERα i ERβ w estrogenozależnej regulacji funkcjonowania wielu tkanek i narządów pośred– niczy receptor estrogenów oddziałujący z białkami G. Powszechne występowa– nie receptora estrogenów oddziałującego z białkami G w różnych tkankach, jak i obserwowana deregulacja jego ekspresji w określonych patologiach pozwala domniemywać o istotnej roli tego receptora w funkcjonowaniu komórek, tkanek i organizmów. Aktywacja/dezaktywacja receptora estrogenów GPER ma miejsce podczas metabolizmu węglowodanów i lipidów czy odpowiedzi immunologicznej, zaangażowana jest w wiele zdarzeń ze strony układu rozrodczego, sercowo– naczyniowego, nerwowego oraz kostnego
The role of mesalazine in the chemoprevention of colorectal cancer
Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in females and the third in males. Every year there are more than a million new cases of colorectal cancer and more than six hundred thousand patients die. The risk factors of colorectal cancer include unhealthy lifestyle, genetic predisposition (found in about 25% of cases) and chronic colon inflammation i.e., ulcerative colitis and Crohn's disease. Many studies suggested the protective effect of nonsteroidal anti-inflammatory drugs, including mesalazine, on the chemoprevention of colorectal cancer. Studies have shown that the regular intake of mesalazine reduces the risk of developing colorectal polyps and cancer by its multidirectional action. Anti-inflammatory mechanisms include the modulation of inflammatory cytokine production, COX inhibition and impact on NF-κB and PPARδ pathways. Consequently, mesalazine inhibits, or at least delays, the processes of carcinogenesis.Rak jelita grubego (RJG) jest czwartym najczęściej rozpoznawanym rakiem u kobiet i trzecim u mężczyzn. Każdego roku stwierdza się ponad milion nowych zachorowań i ponad sześćset tysięcy zgonów z powodu RJG. Do czynników ryzyka RJG zalicza się niezdrowy styl życia, predyspozycje genetyczne (stwierdzane w około 25% przypadków zachorowań) oraz choroby zapalne jelit. Wśród pacjentów z wrzodziejącym zapaleniem jelita grubego i chorobą Leśniowskiego-Crohna występuje podwyższone ryzyko zachorowania na RJG. Wiele badań wykazało ochronne działanie niesteroidowych leków przeciwzapalnych, w tym mesalazyny, w chemoprewencji raka jelita grubego. Badania wykazały, że regularne przyjmowanie mesalazyny - dzięki jej wielokierunkowemu działaniu - powodowało redukcję rozwoju polipów jelita grubego i transformacji nowotworowej komórek jelita grubego. Przeciwzapalne mechanizmy działania mesalazyny polegają na modulowaniu produkcji cytokin zapalnych, hamowaniu cyklooksygenazy oraz odziaływaniu na szlaki sygnałowe z udziałem czynnika transkrypcyjnego NF-κB i receptorów PPARδ. W konsekwencji mesalazyna hamuje, bądź przynajmniej opóźnia, procesy nowotworzenia
High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist
Sex- and Age-Related Estrogen Signaling Alteration in Inflammatory Bowel Diseases: Modulatory Role of Estrogen Receptors
The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor β (ERβ) and ERα spliced variants ERα36 and ERα46 in Crohn’s disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17β-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERβ in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERβ expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERβ expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner