Hydrogen peroxide induces GADD153 in Jurkat cells through the protein kinase C-dependent pathway

Authors: Oh-hashi, Kentaro; Maehara, Kayoko; Isobe, Ken-ichi

Source: Redox Report, Volume 9, Number 3, June 2004 , pp. 173-178(6)

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Abstract:

Growth arrest and DNA damage-inducible gene 153 (GADD153) is a CCAAT/enhancer binding protein (C/EBP) related gene and is induced in response to various stimuli including DNA damaging agents, UV irradiation, and serum starvation. In this study, we investigated which intracellular signals contribute to the expression of GADD153 mRNA in Jurkat cells in response to oxidative stress using several kinds of kinase inhibitors. GADD153 mRNA expression was immediately enhanced following hydrogen peroxide exposure and was significantly inhibited by treatment with H-7, staurosporin, and Ro-31-8220. In particular, rottlerin, a PKC? specific inhibitor, markedly attenuated hydrogen peroxide-induced GADD153 mRNA expression even at 1 ?M. Treatment with a potent PKC activator, phorbol-12-myristate-13-acetate (PMA), augmented GADD153 mRNA in Jurkat cells in the presence of hydrogen peroxide, although PMA alone induced GADD153 mRNA marginally. Hydrogen peroxide significantly enhanced the AP-1 binding activity of the nuclear extract from Jurkat cells to the GADD153 AP-1 binding site. AP-1 binding activity was suppressed by rottlerin treatment. These findings indicate that PKC, especially PKC?, plays an important role in the induction of GADD153 mRNA following oxidative stress.

Keywords: HYDROGEN PEROXIDE; JURKAT CELLS; PROTEIN KINASE C; GADD153

Document Type: Research Article

DOI: http://dx.doi.org/10.1179/135100004225005183

Affiliations: Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Aichi, Japan.

Publication date: 2004-06-01

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