Low oxygen supply to tissues, designated as hypoxia, may occur in the context of normal processes (embryogenesis, high altitude living) or in pathological conditions, accompanied by reduced tissue perfusion or low O2 concentration (heart failure, chronic obstructive pulmonary disease, inflammatory processes, cancer). The response to hypoxia is mainly achieved through the action of hypoxia-inducible transcription factors (Hypoxia Inducible Factors -HIFs), which regulate processes such as

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... esis, inflammatory response, metabolism, cellular proliferation and survival. HIFs are heterodimers whose action is mainly controlled through the regulation of their α subunit. HIF-1α is expressed in all tissues and cell types and is mainly regulated post-transcriptionally. Hydrogen sulfide (H2S) is the most recently recognized gasotransmitter. H2S modifies proteins involved in various processes, such as apoptosis, ATP production, cell proliferation, production of free radicals and antioxidants, affecting many pathological conditions. No consistent data regarding the effect of H2S on the regulation of HIF-1α are currently available. The aim of this work was to investigate the effect of H2S on the response of A549 lung adenocarcinoma cells to hypoxia, through the administration of the H2S donor GYY4137 and the endogenous H2S producing enzyme CSE inhibitor propargylglycine (PPG). To this end, the effect of the aforementioned factors on HIF-1α protein levels, HIF-1 transcriptional activity and cell survival and proliferation under normoxia and hypoxia were studied. The results of the present study showed that exogenous H2S administration did not affect HIF-1α levels, HIF-1 transcriptional activity, and viability of A549 cells. In contrast, inhibition of CSE decreased HIF-1α levels and HIF-1 transcriptional activity. The above results indicate that endogenously produced hydrogen sulfide is necessary and sufficient to induce transcriptionally active HIF-1α under hypoxic conditions. mTOR (mammalian target of rapamycin): υποδοχέας της ραπαμυκίνης στα θηλαστικά MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium Na2S (sodium sulfide): θειούχο νάτριο NADH (Nicotinamide adenine dinucleotide): νικοτιναμίδο-αδενίνο-δινουκλεοτίδιο NASH (sodium hydrosulfide): όξινο θειούχο νάτριο NF-κΒ (nuclear factor kappa-light-chain-enhancer of activated B cells): πυρηνικός παράγοντας ενισχυτής των κάππα ελαφριών αλυσίδων των B κυττάρων NLS (Nuclear Localization Signal): σήμα πυρηνικού εντοπισμού NO (Nitric Oxide): Μονοξείδιο του αζώτου NOS (Nitric Oxide Synthase): Συνθάση του μονοξειδίου του αζώτου Nrf2: Nuclear factor erythroid 2-related factor 2 ODD (Oxygen Dependent Degradation domain): περιοχή οξυγονοεξαρτώμενης αποικοδόμησης PAGE (Polyacrylamide gel electrophoresis): Ηλεκτροφόρηση σε πηκτή πολυακρυλαμιδίου PAS: PER-ARNT-SIM PBS (phosphate buffered saline): Διάλυμα φυσιολογικής συγκέντρωσης φωσφορικών ιόντων PCAF (p300/CBP-associated factor): παράγοντας σχετιζόμενος με το σύμπλεγμα p300/CBP PDGF (Platelet Derived Growth Factor): αυξητικός παράγοντας αιμοπεταλίων PERK (Protein kinase RNA-like ER kinase): κινάση του ενδοπλασματικού δικτύου όμοια με την ενεργοποιούμενη από το RNA κινάση PGF (Placental Growth Factor): Πλακουντιακός αυξητικός παράγοντας PHD (Prolyl Hydroxylase): προλυλ-υδροξυλάση PI3K (phosphatidyl inositol-4,5 bisphosphate-3-kinase): κινάση της 4,5 διφωσφορικής φωσφατιδυλινοσιτόλης PLP (Pyridoxal Phosphate): Φωσφορική πυριδοξάλη PMSF (phenylmethylsulfoxide fluoride): φαινυλμεθυλ-φθοριούχος εστέρας του σουλφονικού οξέος) PPG/PAG (DL-propargylglycine): Προπάργυλγλυκίνη PTEN (phosphatase and tensin homolog): πρωτεϊνη ομόλογη φωσφατάσης και τενσίνης PTP1B (Protein Tyrosine Phosphatase 1B): τυροσινική φωσφατάση 1Β RACK1 (receptor of activated protein kinase C): υποδοχέας της ενεργοποιημένης πρωτεϊνικής κινάσης C ROS (Reactive Oxygen Species): Δραστικές ρίζες οξυγόνου SAM (S-adenosylmethionine): S-αδενοσυλο-μεθειονίνη