TY - JOUR AU - Balogh, Bálint AU - Vecsernyés, Mónika AU - Stayer-Harci, Alexandra AU - Berta, Gergely AU - Tarjányi, Oktávia AU - Sétáló, György (ifj.) TI - Urocortin stimulates the ERK1/2 signaling pathway and the proliferation of HeLa cells via CRF receptor 1 JF - FEBS OPEN BIO J2 - FEBS OPEN BIO VL - 13 PY - 2023 IS - 5 SP - 818 EP - 832 PG - 15 SN - 2211-5463 DO - 10.1002/2211-5463.13602 UR - https://m2.mtmt.hu/api/publication/33728557 ID - 33728557 AB - Corticotropin-releasing factor (CRF) stimulates adrenocorticotropic hormone (ACTH) secretion from the pituitary gland and is an essential regulator of the hypothalamic-pituitary-adrenocortical axis. Isoforms of CRF receptor are known to mediate the effects of urocortin stress ligands on the regulation of stress responses, anxiety, and feeding behavior; however, urocortin stress ligands also influence cell proliferation. In view of the tumor-promoting capacity of prolonged stress, here we investigated (a) the effect of urocortin on cell proliferative signaling via extracellular signal-regulated kinase 1/2, (b) the expression and cellular distribution of the specific CRF receptor isoforms, and (c) the intracellular localization of phosphorylated ERK1/2 in HeLa cells. Stimulation of cell proliferation was observed in the presence of 10 nm urocortin. Our data also suggest that MAP kinase MEK, the transcription factors E2F-1 and p53, and PKB/Akt are involved in this process. These findings may have therapeutic relevance for the targeted treatment of various malignancies. LA - English DB - MTMT ER - TY - JOUR AU - Tarjányi, Oktávia AU - Haerer, Julian AU - Vecsernyés, Mónika AU - Berta, Gergely AU - Stayer-Harci, Alexandra AU - Balogh, Bálint AU - Borbásné Farkas, Kornélia AU - Boldizsár, Ferenc AU - Szeberényi, József AU - Sétáló, György (ifj.) TI - Prolonged treatment with the proteasome inhibitor MG-132 induces apoptosis in PC12 rat pheochromocytoma cells JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 12 PY - 2022 IS - 1 PG - 14 SN - 2045-2322 DO - 10.1038/s41598-022-09763-z UR - https://m2.mtmt.hu/api/publication/32766373 ID - 32766373 AB - Rat pheochromocytoma (PC12) cells were treated with the proteasome inhibitor MG-132 and morphological changes were recorded. Initially, neuronal differentiation was induced but after 24 h signs of morphological deterioration became apparent. We performed nuclear staining, flow cytometry and WST-1 assay then analyzed signal transduction pathways involving Akt, p38 MAPK (Mitogen-Activated Protein Kinase), JNK (c-Jun N-terminal Kinase), c-Jun and caspase-3. Stress signaling via p38, JNK and c-Jun was active even after 24 h of MG-132 treatment, while the survival-mediating Akt phosphorylation declined and the executor of apoptosis (caspase-3) was activated by that time and apoptosis was also observable. We examined subcellular localization of stress signaling components, applied kinase inhibitors and dominant negative H-Ras mutant-expressing PC12 cells in order to decipher connections of stress-mediating pathways. Our results are suggestive of that treatment with the proteasome inhibitor MG-132 has a biphasic nature in PC12 cells. Initially, it induces neuronal differentiation but prolonged treatments lead to apoptosis. LA - English DB - MTMT ER - TY - JOUR AU - Balogh, Bálint AU - Vecsernyés, Mónika AU - Veres-Székely, Apor AU - Berta, Gergely AU - Stayer-Harci, Alexandra AU - Tarjányi, Oktávia AU - Sétáló, György (ifj.) TI - Urocortin stimulates ERK1/2 phosphorylation and proliferation but reduces ATP production of MCF7 breast cancer cells JF - MOLECULAR AND CELLULAR ENDOCRINOLOGY J2 - MOL CELL ENDOCRINOL VL - 547 PY - 2022 PG - 16 SN - 0303-7207 DO - 10.1016/j.mce.2022.111610 UR - https://m2.mtmt.hu/api/publication/32709502 ID - 32709502 LA - English DB - MTMT ER - TY - JOUR AU - Czigler, András AU - Tóth, Luca AU - Szarka, Nikolett AU - Szilágyi, Krisztina AU - Kellermayer, Zoltán AU - Stayer-Harci, Alexandra AU - Vecsernyes, Monika AU - Ungvári, Zoltán István AU - Szolics, Alex AU - Koller, Ákos AU - Büki, András AU - Tóth, Péter József TI - Prostaglandin E2, a postulated mediator of neurovascular coupling, at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles JF - PROSTAGLANDINS & OTHER LIPID MEDIATORS J2 - PROSTAG OTH LIPID M VL - 146 PY - 2020 PG - 7 SN - 1098-8823 DO - 10.1016/j.prostaglandins.2019.106389 UR - https://m2.mtmt.hu/api/publication/30886434 ID - 30886434 AB - There is considerable controversy regarding the vasoactive action of prostaglandin E2 (PGE2). On the one hand, indirect evidence implicates that astrocytic release of PGE2 contributes to neurovascular coupling responses mediating functional hyperemia in the brain. On the other hand, overproduction of PGE2 was also reported to contribute to cerebral vasospasm associated with subarachnoid hemorrhage. The present study was conducted to resolve this controversy by determining the direct vasoactive effects of PGE2 in resistance-sized human cerebral parenchymal arterioles. To achieve this goal PGE2-induced isotonic vasomotor responses were assessed in parenchymal arterioles isolated from fronto-temporo-parietal cortical tissues surgically removed from patients and expression of PGE2 receptors were examined. In functionally intact parenchymal arterioles lower concentrations of PGE2 (from 10-8 to 10-6 mol/l) caused significant, endothelium-independent vasorelaxation, which was inhibited by the EP4 receptor blocker BGC201531. In contrast, higher concentrations of PGE2 evoked significant EP1-dependent vasoconstriction, which could not be reversed by the EP4 receptor agonist CAY10598. We also confirmed previous observations that PGE2 primarily evokes constriction in intracerebral arterioles isolated from R. norvegicus. Importantly, vascular mRNA and protein expression of vasodilator EP4 receptors was significantly higher than that of vasoconstrictor EP1 receptors in human cerebral arterioles. PGE2 at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles. This bimodal vasomotor response is consistent with both the proposed vasodilator role of PGE2 during functional hyperemia and its putative role in cerebral vasospasm associated with subarachnoid hemorrhage in human patients. LA - English DB - MTMT ER - TY - GEN AU - Stayer-Harci, Alexandra AU - Balogh, Bálint AU - Berta, Gergely AU - Tarjányi, Oktávia AU - Vecsernyés, Mónika AU - Ábrahám, Hajnalka AU - Szeberényi, József AU - Sétáló, György (ifj.) TI - Az urokortin2 jelátviteli kapcsolatainak vizsgálata PC12 sejtekben PY - 2015 UR - https://m2.mtmt.hu/api/publication/2952364 ID - 2952364 N1 - [Poszter] LA - Hungarian DB - MTMT ER - TY - CHAP AU - Stayer-Harci, Alexandra AU - Mátics, Róbert AU - Varga, Dániel AU - Pollák, Edit AU - Varga, Máté ED - Rauch, Tibor ED - Varga, Máté ED - Hoffmann, Gyula TI - A sejtek progresszív determinációja T2 - Fejlődésbiológia II PB - PTE Természettudományi Kar CY - Pécs SN - 9786155339998 PY - 2014 SP - 311 EP - 350 PG - 40 UR - https://m2.mtmt.hu/api/publication/3322990 ID - 3322990 LA - Hungarian DB - MTMT ER - TY - CHAP AU - Varga, Máté AU - Varga, Sándor AU - Szatmári, Dávid Zoltán AU - Gálosi, Rita AU - Stayer-Harci, Alexandra ED - Rauch, Tibor ED - Varga, Máté ED - Hoffmann, Gyula TI - Indukció és determináció T2 - Fejlődésbiológia II PB - PTE Természettudományi Kar CY - Pécs SN - 9786155339998 PY - 2014 SP - 351 EP - 398 PG - 48 UR - https://m2.mtmt.hu/api/publication/3321697 ID - 3321697 LA - Hungarian DB - MTMT ER - TY - CHAP AU - Schipp, Renáta AU - Stayer-Harci, Alexandra AU - Kiss, Katalin AU - Németh, Zoltán AU - Mátics, Róbert AU - Barna, János AU - Hoffmann, Gyula AU - Varga, Dániel AU - Varga, Máté AU - Varga, Judit ED - Rauch, Tibor ED - Varga, Máté ED - Hoffmann, Gyula TI - A sejtek kommunikációja és kölcsönhatásai, jelátviteli folyamatok, jelátvitel és sejthalál T2 - Fejlődésbiológia II PB - PTE Természettudományi Kar CY - Pécs SN - 9786155339998 PY - 2014 SP - 171 EP - 218 PG - 48 UR - https://m2.mtmt.hu/api/publication/2729810 ID - 2729810 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Tarjányi, Oktávia AU - Berta, Gergely AU - Stayer-Harci, Alexandra AU - Bacsa, EB AU - Stark, B AU - Pap, Marianna AU - Szeberényi, József AU - Sétáló, György (ifj.) TI - The role of Src protein in the process formation of PC12 cells induced by the proteasome inhibitor MG-132. JF - NEUROCHEMISTRY INTERNATIONAL J2 - NEUROCHEM INT VL - 63 PY - 2013 IS - 5 SP - 413 EP - 422 PG - 10 SN - 0197-0186 DO - 10.1016/j.neuint.2013.07.008 UR - https://m2.mtmt.hu/api/publication/2376069 ID - 2376069 AB - The PC12 (rat pheochromocytoma) cell line is a popular model system to study neuronal differentiation. Upon prolonged nerve growth factor (NGF) exposure these tumor cells stop to divide, become polygonal, grow projections and start to look and behave like sympathetic neurons. Differentiation of PC12 cells can also be induced by peptidyl-aldehyde proteasome inhibitors, such as Z-Leu-Leu-Leu-al (also known as MG-132) or via infection of the cells with Rous sarcoma virus. The signal transduction pathways underlying process formation, however, are still not fully understood. The liganded NGF receptor initiates a protein kinase cascade a member of which is Extracellular Signal-Regulated Kinase (ERK). Active ERK1/2 enzymes phosphorylate various cytoplasmic proteins and can also be translocated into the nucleus, where they regulate gene expression by activating key transcription factors. Using immunological methods we detected phosphorylation of TrkA, prolonged activation of Src, and ERK1/2 with nuclear translocation of the latter during MG-132-induced process formation of PC12 cells. Activated Src remained predominantly cytoplasmic. MG-132-induced sustained ERK1/2 activation, nuclear translocation and neuritogenesis required the intact function of Src since these phenomena were markedly reduced or failed upon chemical inhibition of Src tyrosine protein kinase activity. LA - English DB - MTMT ER - TY - JOUR AU - Berta, Gergely AU - Stayer-Harci, Alexandra AU - Tarjányi, Oktávia AU - Vecsernyes, M AU - Balogh, András AU - Pap, Marianna AU - Szeberényi, József AU - Sétáló, György (ifj.) TI - Partial rescue of geldanamycin-induced TrkA depletion by a proteasome inhibitor in PC12 cells. JF - BRAIN RESEARCH J2 - BRAIN RES VL - 1520 PY - 2013 SP - 70 EP - 79 PG - 10 SN - 0006-8993 DO - 10.1016/j.brainres.2013.05.015 UR - https://m2.mtmt.hu/api/publication/2330540 ID - 2330540 AB - In this work we tried to identify mechanisms that could explain how chemical inhibition of heat-shock protein 90 reduces nerve growth factor signaling in rat pheochromocytoma PC12 cells. Geldanamycin is an antibiotic originally discovered based on its ability to bind heat-shock protein 90. This interaction can lead to the disruption of heat-shock protein 90-containing multimolecular complexes. It can also induce the inhibition or even degradation of partner proteins dissociated from the 90kDa chaperone and, eventually, can cause apoptosis, for instance, in PC12 cells. Before the onset of initial apoptotic events, however, a marked decrease in the activity of extracellular signal-regulated kinases ERK 1/2 and protein kinase B/Akt can be observed together with reduced expression of the high affinity nerve growth factor receptor, tropomyosine-related kinase, TrkA, in this cell type. The proteasome inhibitor MG-132 can effectively counteract the geldanamycin-induced reduction of TrkA expression and it can render TrkA and ERK1/2 phosphorylation but not that of protein kinase B/Akt by nerve growth factor again inducible. We have found altered intracellular distribution of TrkA in geldanamycin-treated and proteasome-inhibited PC12 cells that may, at least from the viewpoint of protein localization explain why nerve growth factor remains without effect on protein kinase B/Akt. The lack of protein kinase B/Akt stimulation by nerve growth factor in turn reveals why nerve growth factor treatment cannot save PC12 cells from geldanamycin-induced programmed cell death. Our observations can help to better understand the mechanism of action of geldanamycin, a compound with strong human therapeutical potential. LA - English DB - MTMT ER -