Role of intracellular calcium mobilization and cell-density-dependent signaling in oxidative-stress-induced cytotoxicity in HaCaT keratinocytes

Edina Bakondi, M. Gönczi, Éva Szabó, P. Bai, Pál Pacher, P. Gergely, László Kovács, J. Hunyadi, Csaba Szabó, L. Csernoch, L. Virag

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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 molecular 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.

Original languageEnglish
Pages (from-to)88-95
Number of pages8
JournalJournal of Investigative Dermatology
Volume121
Issue number1
DOIs
Publication statusPublished - Jul 1 2003

Fingerprint

Peroxynitrous Acid
Oxidative stress
Cytotoxicity
Keratinocytes
Oxidative Stress
Cell Count
Calcium
Poly(ADP-ribose) Polymerases
Hydrogen Peroxide
Chemical activation
Noxae
Sunburn
Cytoprotection
Poisons
Contact Dermatitis
Erythema
Caspases
Chelation
Superoxides
Nitric Oxide

Keywords

  • Apoptosis
  • Calcium signaling
  • Hydrogen peroxide
  • Necrosis
  • Peroxynitrous acid

ASJC Scopus subject areas

  • Dermatology

Cite this

Role of intracellular calcium mobilization and cell-density-dependent signaling in oxidative-stress-induced cytotoxicity in HaCaT keratinocytes. / Bakondi, Edina; Gönczi, M.; Szabó, Éva; Bai, P.; Pacher, Pál; Gergely, P.; Kovács, László; Hunyadi, J.; Szabó, Csaba; Csernoch, L.; Virag, L.

In: Journal of Investigative Dermatology, Vol. 121, No. 1, 01.07.2003, p. 88-95.

Research output: Contribution to journalArticle

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AU - Gönczi, M.

AU - Szabó, Éva

AU - Bai, P.

AU - Pacher, Pál

AU - Gergely, P.

AU - Kovács, László

AU - Hunyadi, J.

AU - Szabó, Csaba

AU - Csernoch, L.

AU - Virag, L.

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