Journal Article

Gap junctional intercellular communication and cellular response to heat stress

Nobuyuki Hamada, Seiji Kodama, Keiji Suzuki and Masami Watanabe

in Carcinogenesis

Volume 24, issue 11, pages 1723-1728
Published in print November 2003 | ISSN: 0143-3334
Published online November 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg135
Gap junctional intercellular communication and cellular response to heat stress

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Gap junctional intercellular communication (GJIC) is essential in the maintenance of tissue homeostasis and has been implicated in tumor suppression. Recent studies have indicated that GJIC is also involved in cellular stress responses to low dose ionizing radiation, UV light and hydrogen peroxide. However, the contribution of GJIC to the heat stress response has not yet been elucidated. We here demonstrate a potential link between GJIC and the heat stress response. First, we investigated whether the abolition of GJIC by lindane affects heat sensitivity in normal human cells. Lindane potentiated cell killing by heat shock at 43°C, whereas little or no cytotoxicity was observed at 37°C. Nuclear translocation of heat shock protein 72 (HSP72) was interrupted by lindane, although its induction was not affected. These results indicate that lindane exacerbates hyperthermic lethality via disrupted nuclear translocation of HSP72 protein. Second, we assessed whether heat shock alters GJIC and phosphorylation of gap junction connexin (Cx) proteins in normal human cells. Persistent heat treatment augmented Cx43 phosphorylation in a heat- and time-dependent fashion and this phosphorylation was recovered after heat shock. GJIC was also disturbed by heat shock. These results indicate that heat shock augments Cx43 phosphorylation leading to GJIC abrogation. Our present results imply that GJIC contributes to protection against heat stress and that loss of GJIC function during carcinogenesis exacerbates hyperthermic lethality.

Keywords: Cx, connexin; GJIC, gap junctional intercellular communication; HSP, heat shock protein; MAPK, mitogen-activated protein kinase; PKC, protein kinase C

Journal Article.  3947 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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