Identification of multiple transcripts for antioxidant protein 2 (Aop2):: differential regulation by oxidative stress and growth factors

Antioxidant protein 2 is a unique member of the thiol-specific antioxidant family of proteins known to reduce reactive oxygen species in the presence of thiol-containing electron donors. It is also a candidate atherosclerosis susceptibility gene in mice. In the present study, we sought to characterize the transcripts of this gene, and determine which, if any, are regulated by conditions associated with oxidative stress. We have identified multiple Aop2 transcripts by Northern blot, each exhibiting a unique tissue distribution. These include the previously reported 1.47 kb major transcript, two alternative Aop2 transcripts found exclusively in liver, and a testis-specific transcript believed to be the highly related intronless gene Aop2-rs1. Treatment of a murine hepatocyte cell line with glucose oxidase led to the specific and transient induction of the 1.47 kb transcript, while the 3.1 kb transcript was regulated by serum deprivation and re-stimulation with either keratinocyte growth factor or serum in a time-dependent manner. Since these ROS-inducing stimuli involve different mechanisms of action and cellular responses, our data suggest that alternative Aop2 transcripts may play distinct roles in different oxidative stress responses, and possibly in atherosclerosis.