Hibernation induces oxidative stress and activation of NF-kappa B in ground squirrel intestine

Dramatic changes in blood how occur during torpor-arousal cycles in mammali an hibernators that could increase the risk of oxidative stress to sensitiv e tissues. We used 13-lined ground squirrels (Spermophilus tridecemlineatus ) to determine the effect of hibernation on lipid peroxidation and expressi on of stress-activated signaling pathways in the intestine, a tissue highly susceptible to ischemia-reperfusion injury. Compared with summer-active sq uirrels, levels of the mitochondrial stress protein GRP75 were consistently higher in intestinal mucosa of hibernators in each of five hibernation sta tes (entrance, short-bout torpid, long-bout torpid, arousal and interbout e uthermia). The redox-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB), was strongly activated in each hibernation state compared with summer squirrels except for squirrels during an arousal from torpor. In co ntrast, NF-kappaB activation in brown adipose tissue (BAT) was low in activ e and hibernating squirrels regardless of season. Levels of conjugated dien es (products of lipid peroxidation) were higher in intestine of hibernators entering torpor and early in a torpor bout compared with summer squirrels. Conjugated diene levels were also higher in short-bout torpid vs arousing squirrels. The results suggest that the intestinal mucosa is vulnerable to oxidative stress during the hibernation season and in response may activate cellular defense pathways that help minimize severe oxidative damage induc ed by torpor-arousal cycles.