p38 MAPK regulation of transcription factor targets in muscle and heart of the hibernating bat, Myotis lucifugus

Abstract

Mammalian hibernation combines a profound net metabolic rate suppression with the selective up-regulation of key genes whose protein products address specific metabolic needs of the hibernator. The signal transduction pathways and transcription factors involved in regulating hibernation-responsive gene expression are of great interest. The present study suggests an important role for the p38 mitogen-activated protein kinase (p38 MAPK) and selected downstream transcription factors under its control (CREB, ATF-2, Elk-1) in the metabolic response by skeletal muscle during hibernation of little brown bats, Myotis lucifugus. Western blotting was used to quantify both total protein and levels of the phosphorylated, active forms of p38 MAPK, CREB, ATF-2 and Elk-1 in both skeletal muscle and heart of euthermic and hibernating bats. The p38 MAPK pathway was not apparently activated in heart during torpor but skeletal muscle showed strong increases (2.2-11-fold) in the amounts of phosphorylated p38 T180/Y182, CREB S133, ATF-2T69/71 and Elk-1(S383) in the torpid versus aroused state. By contrast both total and phosphorylated levels of Elk-1 in heart were reduced during hibernation to just 30% of the euthermic values. These data implicate p38 MAPK and its transcription factor targets, CREB, ATF-2 and Elk-1 in skeletal muscle maintenance during hibernation.