Regulation of protein synthesis in lymphoblastoid cells during inhibition of cell proliferation by human inteferons

Abstract

Treatment of human lymphoblastoid (Daudi) cells with interferons inhibits cell proliferation in culture within 24 h. The failure of cell growth has been shown to be associated with impaired processing and decreased stability of newly replicated DNA. Because there is a close relationship between DNA replication and protein synthesis we have measured protein synthesis in intact Daudi cells. Protein synthesis declined steadily between 24 and 96 h after interferon treatment to a value which is only 20–30% of the rate in control cells. The enzyme 2′,5′‐oligo(A) synthetase is induced but our data do not support a role for the 2′,5′‐oligo(A)‐activated ribonuclease in the control of translation in this system.

Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis

“…Thus strains of E. coli that produce SLT-1 have all the necessary components to elicit EC apoptosis, namely a sensitizing agent, SLT-1, and an inducer of apoptosis, LPS. Other naturally occurring agents reported to have protein synthesis inhibitory properties include Pseudomonas aeruginosa toxin (101), interferons (39), and TNF-␣ (129). The role of these agents in sensitizing ECs to LPS-induced apoptosis during mixed infection and inflammation should be considered.…”

Regulation of cell proliferation and differentiation by interferons

“…Regulation ofprotein synthesis in interferon-treated cells Although the role of protein synthesis inhibition in the antiviral effects of interferons has been widely studied, there are surprisingly few detailed reports on changes in translational activity during the regulation of proliferation of uninfected cells. Some studies have shown decreased incorporation of radioactive amino acids into total cell protein in interferon-treated fibroblasts and Daudi cells (Fuse & Kawata, 1976; Pfeffer et al, 1979;Clemens et al, 1984). On the other hand, there appears to be little or no inhibition of protein synthesis during impairment of growth in other cell types (Tovey et al, 1975;Fuse & Kuwata, 1977;Panniers & Clemens, 1981).…”

“…The interpretation of some of these results is, however, complicated by technical considerations. Inhibition of protein synthesis in uninfected cells appears to be a relatively late response to interferon treatment, often requiring 24-48 h to develop (Clemens et al, 1984). Furthermore, the conditions of culture used during the measurements may influence the rates of protein synthesis observed.…”

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells

“…]leucine (New England Nuclear) was measured by trichloroacetic acid precipitation of protein as described previously [11,12,16,18]. The concentrations and specific radioactivities of these precursors are given in the legends.…”

“…On the other hand,-inhibition of incorporation of labelled amino acids has been observed in some systems in which cell proliferation is inhibited [7][8][9]. The human lymphoblastoid Daudi cell line is extremely sensitive in exhibiting a marked suppression of growth when human interferons are added in culture [10][11][12]. We have investigated, using this system, the extent to which the changes in growth rate can be correlated with changes in protein synthesis.…”