AMBIENT-TEMPERATURE REGULATION OF APOPTOSIS IN BROWN ADIPOSE-TISSUE -ERK1 2 PROMOTES NOREPINEPHRINE-DEPENDENT CELL-SURVIVAL/

Brown adipose tissue hyperplasia is a fundamental response to low ambi ent temperature. We show here that cold exposure of an animal markedly increased the phosphorylation of mitogen-activated protein kinase (p4 2/p44) Erk1 and Erk2 in brown adipose tissue, and protected cells in t he tissue from apoptosis, We also show that cessation of the sympathet ic stimulus, by transferring cold-adapted animals to 28 degrees C, cau sed an increased rate of apoptosis in the tissue. In primary cultures of brown adipose tissue, norepinephrine (NE) stimulated both the phosp horylation and the activity of Erk1/2 via the Erk kinase MEK, and prot ected the cells form apoptosis. Similarly, agonist stimulation of alph a(1)- and beta-adrenergic receptors and increases in the intracellular level of Ca2+ and cAMP stimulated the phosphorylation of Erk1/2, Agon ist stimulation of alpha(1) and beta-adrenergic receptors, and increas ed intracellular cAMP level also promoted the cell survival. Furthermo re, NE stimulated the expression and secretion of basic fibroblast gro wth factor (bFGF), which further promoted the cell survival via MEK-de pendent activation of Erk1/2. In essence, we show that Erk1/2 has a cr itical role in promoting NE- and bFGF dependent survival of brown adip ocytes, and propose that NE- and bFGF-dependent regulation of the cell survival is involved in the cold-induced hyperplasia of brown adipose tissue.