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 ambient temperature. We show here that cold exposure of an animal markedly increased the phosphorylation of mitogen-activated protein kinase (p42/p44) Erk1 and Erk2 in brown adipose tissue, and protected cells in the tissue from apoptosis. We also show that cessation of the sympathetic stimulus, by transferring cold-adapted animals to 28 degreesC, caused an increased rate of apoptosis in the tissue. In primary cultures of brown adipose tissue, norepinephrine (NE) stimulated both the phosphorylation and the activity of Erk1/2 via the Erk kinase MEK, and protected the cells form apoptosis. Similarly, agonist stimulation of alpha1- and beta-adrenergic receptors and increases in the intracellular level of Ca2+ and cAMP stimulated the phosphorylation of Erk1/2. Agonist stimulation of alpha1- and beta-adrenergic receptors, and increased intracellular cAMP level also promoted the cell survival. Furthermore, NE stimulated the expression and secretion of basic fibroblast growth factor (bFGF), which further promoted the cell survival via MEK-dependent activation of Erk1/2. In essence, we show that Erk1/2 has a critical role in promoting NE- and bFGF-dependent survival of brown adipocytes, and propose that NE- and bFGF-dependent regulation of the cell survival is involved in the cold-induced hyperplasia of brown adipose tissue.
Lindquist
J M
JM
The Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, S-106 91 Stockholm, Sweden.
Rehnmark
S
S
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003080:Cold Temperature; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009638:Norepinephrine / Q000494:pharmacology*; D010766:Phosphorylation; D011941:Receptors, Adrenergic / Q000378:metabolism; D013696:Temperature
D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D016222:Fibroblast Growth Factor 2; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium; D009638:Norepinephrine