Lindquist J M, Rehnmark S
The Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, S-106 91 Stockholm, Sweden.
J Biol Chem. 1998 Nov 13;273(46):30147-56. doi: 10.1074/jbc.273.46.30147.
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.
棕色脂肪组织增生是对环境低温的一种基本反应。我们在此表明，动物暴露于寒冷环境会显著增加棕色脂肪组织中丝裂原活化蛋白激酶（p42/p44）Erk1和Erk2的磷酸化，并保护组织中的细胞免于凋亡。我们还表明，将适应寒冷的动物转移至28摄氏度以停止交感神经刺激，会导致该组织中凋亡率增加。在棕色脂肪组织的原代培养中，去甲肾上腺素（NE）通过Erk激酶MEK刺激Erk1/2的磷酸化和活性，并保护细胞免于凋亡。同样，α1和β肾上腺素能受体的激动剂刺激以及细胞内Ca2+和cAMP水平的升高会刺激Erk1/2的磷酸化。α1和β肾上腺素能受体的激动剂刺激以及细胞内cAMP水平的升高也促进细胞存活。此外，NE刺激碱性成纤维细胞生长因子（bFGF）的表达和分泌，后者通过MEK依赖的Erk1/2激活进一步促进细胞存活。本质上，我们表明Erk1/2在促进棕色脂肪细胞依赖NE和bFGF的存活中起关键作用，并提出细胞存活的NE和bFGF依赖性调节参与了寒冷诱导的棕色脂肪组织增生。
