Gap junctions: The 'kiss of death' and the 'kiss of life'

A. F. Andrade-Rozental, R. Rozental, M. G. Hopperstad, J. K. Wu, F. D. Vrionis, David C. Spray

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Cells expressing herpes simplex-thymidine kinase (HSV-tk) can be killed 'in vitro' within 5 days of treatment with 20 μM ganciclovir (GCV) and transmit this toxicity to adjacent cells lacking HSV-tk; this phenomenon was termed 'bystander effect' or 'kiss of death'. On testing a large number of cell lines in vitro, a wide range of sensitivity to GCV-mediated bystander killing has been reported. Although intercellular transfer of GCV metabolites through gap junction channels seems to be a likely mechanism for the 'kiss of death', some studies suggest that other pathways may contribute to induced apoptosis of neighboring cells. To further investigate the mechanism underlying cell death mediated by HSV-tk and to evaluate the efficacy of gap junction channels formed by different connexins in this process, we have stably transfected a virtually uncoupled mouse neuroblastoma cell line (N2A cells) with different connexin-types expressed by neural cells (Cx32, Cx37, Cx40, Cx43) and co-cultured these cells with N2A cells stably transfected with Cx37 and HSV-tk. Here, we confirm our previous studies and those of others that the extent of cell death and sensitivity to GCV depend on the degree of connexin expression in transfectants. Further, we show that the bystander effect also depends on which connexin is expressed; reported disparities regarding the extent of GCV-mediated cellular apoptosis are likely due both to the degree of functional coupling and the type of connexin expressed. These results support the notion that gap junction hemichannels formed of certain connexins are more likely than others to pair functionally with Cx37, and suggest co-transfection strategies that might prove effective in sensitizing tumor cell populations to GCV. In addition, potential applications are discussed for use of the 'good Samaritan effect', a mechanism by which bystander cells have been suggested to prevent cytotoxicity. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)308-315
Number of pages8
JournalBrain Research Reviews
Volume32
Issue number1
DOIs
StatePublished - Mar 24 2000

Fingerprint

Gap Junctions
Ganciclovir
Connexins
Bystander Effect
Cell Death
Apoptosis
Cell Line
Connexin 43
Herpes Simplex
Thymidine Kinase
Neuroblastoma
Transfection
Cultured Cells
Population

Keywords

  • Apoptosis
  • Bystander effect
  • Cx32
  • Cx37
  • Cx40
  • Cx43
  • Gap junction
  • Good Samaritan effect
  • Intercellular communication

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Andrade-Rozental, A. F., Rozental, R., Hopperstad, M. G., Wu, J. K., Vrionis, F. D., & Spray, D. C. (2000). Gap junctions: The 'kiss of death' and the 'kiss of life'. Brain Research Reviews, 32(1), 308-315. https://doi.org/10.1016/S0165-0173(99)00099-5

Gap junctions : The 'kiss of death' and the 'kiss of life'. / Andrade-Rozental, A. F.; Rozental, R.; Hopperstad, M. G.; Wu, J. K.; Vrionis, F. D.; Spray, David C.

In: Brain Research Reviews, Vol. 32, No. 1, 24.03.2000, p. 308-315.

Research output: Contribution to journalArticle

Andrade-Rozental, AF, Rozental, R, Hopperstad, MG, Wu, JK, Vrionis, FD & Spray, DC 2000, 'Gap junctions: The 'kiss of death' and the 'kiss of life'', Brain Research Reviews, vol. 32, no. 1, pp. 308-315. https://doi.org/10.1016/S0165-0173(99)00099-5
Andrade-Rozental AF, Rozental R, Hopperstad MG, Wu JK, Vrionis FD, Spray DC. Gap junctions: The 'kiss of death' and the 'kiss of life'. Brain Research Reviews. 2000 Mar 24;32(1):308-315. https://doi.org/10.1016/S0165-0173(99)00099-5
Andrade-Rozental, A. F. ; Rozental, R. ; Hopperstad, M. G. ; Wu, J. K. ; Vrionis, F. D. ; Spray, David C. / Gap junctions : The 'kiss of death' and the 'kiss of life'. In: Brain Research Reviews. 2000 ; Vol. 32, No. 1. pp. 308-315.
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