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001-es BibID:	BIBFORM045939
035-os BibID:	PMID:12839568
Első szerző:	Bakondi Edina (biokémikus, vegyész)
Cím:	Role of Intracellular Calcium Mobilization and Cell-Density-Dependent Signaling in Oxidative-Stress-Induced Cytotoxicity in HaCaT Keratinocytes / Edina Bakondi, Mónika Gönczi, Éva Szabó, Péter Bai, Pál Pacher, Pál Gergely, László Kovács, János Hunyadi, Csaba Szabó, László Csernoch, László Virág
Dátum:	2003
ISSN:	0022-202X
Megjegyzések:	Peroxynitrite is a nitric-oxide-derived cytotoxic mediator produced in a broad range of inflammatory conditions, ranging from sunburn erythema to contact hypersensitivity. Our previous work has shown that in HaCaT cells the cytotoxic activity of peroxynitrite involves both apoptotic and necrotic routes with poly(ADP-ribose) polymerase activation serving as a mol-ecular switch diverting the default apoptotic pathway toward necrosis. Nonetheless, keratinocytes are regarded as highly resistant toward environmental noxa including oxidative stress. We set out to investigate the possible role of two parameters, intracellular calcium mobilization and high cell density, in protecting HaCaT cells from peroxynitrite/oxidative-stress-induced cytotoxicity. First we characterized the effect of peroxynitrite on the calcium homeostasis of HaCaT cells and demonstrated that both authentic peroxynitrite and the peroxynitrite generating compound 3-morpholino-sydnonimine triggered an elevation in intracellular calcium levels. Moreover, we established that treatment of cells with the cell-permeable calcium chelator BAPTA-AM provided significant cytoprotection against peroxynitrite- and hydrogen-peroxide-induced cytotoxicity. Furthermore, when cells reached confluence they were highly resistant to the toxic effects of peroxynitrite, hydrogen peroxide, and superoxide. The resistance to oxidative stress provided by calcium chelation and high cell density involved inhibiting the activation of both poly(ADP-ribose) polymerase and caspases. Our data may provide an explanation for the resistance to oxidative stress of superficial, highly differentiated keratinocytes and indicate that basal proliferative keratinocytes are sensitive in vivo targets of oxidative stress injury.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	Journal of Investigative Dermatology. - 121 : 1 (2003), p. 88-95. -
További szerzők:	Gönczi Mónika (1974-) (élettanász) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Bai Péter (1976-) (biokémikus) Pacher Pál Gergely Pál (1947-) (biokémikus) Kovács László (1939-) (élettanász) Hunyadi János (1943-) (bőrgyógyász, kozmetológus, allergológus) Szabó Csaba (1967-) (orvos) Csernoch László (1961-) (élettanász) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
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001-es BibID:	BIBFORM030258
035-os BibID:	WOS:000181565400020
Első szerző:	Magyar János (élettanász)
Cím:	Differential effects of fluoxetine enantiomers in mammalian neural and cardiac tissues / János Magyar, Zoltán Rusznák, Csaba Harasztosi, Ágnes Körtvély, Pál Pacher, Tamás Bányász, Csaba Pankucsi, László Kovács, Géza Szűcs, Péter P. Nánási, Valéria Kecskeméti
Dátum:	2003
ISSN:	1107-3756
Megjegyzések:	Racemic fluoxetine is a widely used SSRI antidepressant compound having also anticonvulsant effect. In addition, it was shown that it blocked several types of voltage gated ion channels including neural and cardiac calcium channels. In the present study the effects of enantiomers of fluoxetine (R(-)-fluoxetine and S(+)-fluoxetine) were compared on neuronal and cardiac voltage-gated Ca2+ channels using the whole cell configuration of patch clamp techniques, and the anticonvulsant action of these enantiomers was also evaluated in a mouse epilepsy model. In isolated pyramidal neurons of the dorsal cochlear nucleus of the rat the effect of fluoxetine (S(+), R(-) and racemic) was studied on the Ca2+ channels by measuring peak Ba2+ current during ramp depolarizations. All forms of fluoxetine reduced the Ba2+ current of the pyramidal cells in a concentration-dependent manner, with a K, value of 22.3 +/- 3.6 muM for racemic fluoxetine. This value of K, was higher by one order of magnitude than found in cardiac myocytes with fluoxetine enantiomers (2.4 +/- 0.1 and 2.8 +/- 0.2 muM). Difference between the effects of the two enantiomers on neuronal Ba2+, current was observed only at 5 muM concentration: R(-)-fluoxetine inhibited 28 +/- 3% of the peak current, while S(+)-fluoxetine reduced the current by 18 +/- 2% (n=13, P<0.05). In voltage clamped canine ventricular cardiomyocytes both enantiomers of fluoxetine caused a reversible concentration-dependent block of the peak Ca2+ current measured at 0 mV. Significant differences between the two enantiomers in this blocking effect was observed at low concentrations only: S(+)-fluoxetine caused a higher degree of block than R(-)-fluoxetine (56.3 +/- 2.2% versus 49.1 +/- 2.2% and 95.5 +/- 0.9% versus 84.5 +/- 3.1% block with 3 and 10 μM S(+) and R(-)-fluoxetine, respectively, P<0.05, n=5). Studied in current clamp mode, micromolar concentrations of fluoxetine shortened action potential duration of isolated ventricular cells, while higher concentrations also suppressed maximum velocity of depolarization and action potential amplitude. This shortening effect was significantly greater in the case of S(+) than R(-)-fluoxetine at 1 and 3 muM concentrations, whereas no differences in their effects on depolarization were observed. In pentylenetetrazole-induced mouse epilepsy model fluoxetine pretreatment significantly increased the 60 min survival rate, survival duration and seizure latency. These effects were more pronounced with the R(-) than the S(+) enantiomer. The results indicate that fluoxetine exerts much stronger suppressive effect on cardiac than neuronal calcium channels. At micromolar concentrations (between 1 and 10 muM) R(-)-fluoxetine is more effective than the S(+) enantiomer on neuronal, while less effective on cardiac calcium channels. The stronger anticonvulsant effect of the R(-) enantiomer may, at least partially, be explained by these differences. Used as an antidepressant or anticonvulsant drug, less severe cardiac side-effects are anticipated with the R(-) enantiomer.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	International Journal of Molecular Medicine. - 11 : 4 (2003), p. 535-542. -
További szerzők:	Rusznák Zoltán (1965-) (élettanász) Harasztosi Csaba Körtvély Ágnes Pacher Pál Bányász Tamás (1960-) (élettanász) Pankucsi Csaba (farmakológus) Kovács László (1939-) (élettanász) Szűcs Géza (1948-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Kecskeméti Valéria
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