Chapter

Recent Advances in Tryptophan Research

Volume 398 of the series Advances in Experimental Medicine and Biology pp 155-159

Tryptophan Starvation is Involved in Human Interferon-Gamma Mediated Apoptosis

  • M. W. TaylorAffiliated withDepartment of Biology, Indiana University
  • , V. K. KonanAffiliated withDepartment of Biology, Indiana University
  • , D. YuAffiliated withDepartment of Biology, Indiana University

* Final gross prices may vary according to local VAT.

Get Access

Abstract

The tryptophan catabolic enzyme, indoleamine 2,3 dioxygenase (IDO), has been shown to be induced in vivo in lungs of mice by bacterial lipopolysaccharide (Yoshida and Hayaishi, 1978), by influenza virus (Yoshida et al., 1979) and by IFN-gamma (IFN-γ) (Carlin et al., 1987, Taylor and Feng 1991). Unlike other interferon responsive genes, this enzyme is not appreciably induced by any of the type I interferons. We (Feng and Taylor 1989) have previously reported that the human cell line ME180 undergoes cell death very rapidly following treatment with IFN-γ. This cell death appears to be the result of starvation for the essential amino acid tryptophan due to the induction of IDO (Feng and Taylor 1989, Ozaki et al., 1988, Aune and Pogue 1989). In ME180 mutants resistant to the antiproliferative effects of IFN-γ, there is no induction of IDO (Feng and Taylor 1989). Moreover the antiproliferative response to IFN-γ can be reversed by the addition of tryptophan back to the medium (Feng and Taylor, 1989, Ozes and Taylor 1993). In this paper we report that the antiproliferative response to IFN-γ results in apoptosis of treated cells, and that tryptophan starvation by itself appears to be sufficient to drive the cell to apoptosis through the same or similar mechanism.