INDUCTION OF HEME OXYGENASE-1 IN LMH CELLS - COMPARISON OF LMH CELLS TO PRIMARY CULTURES OF CHICK-EMBRYO LIVER-CELLS

Heme oxygenase catalyzes the degradation of heme into biliverdin, carb on monoxide, and iron. Two forms of this enzyme, heme oxygenase-1 and -2, have been identified; only heme oxygenase-1 is subject to inductio n by heme, metal ions, and other chemical and physical perturbations ( e.g. drugs, oxidants, and heat shock). Primary chick embryo liver cell s are widely used for the study of heme metabolism because of their ea se of preparation, low cost, and high degree of similarity to human he me metabolism. Nonetheless, this system has some limitations: new cult ures must be prepared every week; the resulting cell populations are n on-homogeneous; and cells are short-lived, limiting the feasible durat ion of time course and transfection studies. LMH cells are the first c hicken hepatoma cell line to be established. The aim of this study was to characterize the regulation of heme oxygenase-1 in LMH cells, and to compare this regulation to that previously described in primary chi ck embryo liver cells. The induction of heme oxygenase-l was assessed by measuring changes in mRNA levels or enzyme activities in response t o several treatments, including heme, heavy metals, sodium arsenite, a nd heat shock, which have been shown to increase the expression of hem e oxygenase. Similarities were observed with respect to regulation of heme oxygenase-l expression in primary hepatocytes and LMH cells. We r eport the first measurable heat shock response of heme oxygenase-1 in CELC or LMH cells; and show that LMH cells are a useful model for the study of heme oxygenase-1 regulation.