Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading.
Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading.
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DOI：
10.1161/01.res.77.3.544
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发表时间：
1995-09
影响因子：
20.1
通讯作者：
R. Decker;M. G. Cook;M. Behnke-Barclay;M. L. Decker
中科院分区：
文献类型：
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作者：
R. Decker;M. G. Cook;M. Behnke-Barclay;M. L. Decker
用重组生长因子处理的培养的成年兔心肌细胞显示对胰岛素和胰岛素样生长因子（IGF）的反应的蛋白质积累（即生长）速率增加，但表皮生长因子、酸性或碱性成纤维细胞生长因子和血小板衍生生长因子未能增加心脏细胞的收缩蛋白质合成或生长。胰岛素和IGF-1通过刺激合成代谢同时抑制分解代谢途径来增加生长速率，而IGF-2通过明显抑制溶酶体蛋白水解来适度地增加生长。针对IGF-1或IGF-2或IGF结合蛋白3的中和抗体阻断蛋白质积累。针对IGF-1受体的单克隆抗体也抑制重组人IGF-1引起的蛋白质周转的变化，但不抑制IGF-2。在测试的其他生长因子中，只有转化生长因子-β 1增加肌球蛋白重链（MHC）合成的分数速率，β-MHC合成升高，α-MHC合成受到抑制。然而，其他生长因子能够适度刺激该制剂中的DNA合成速率。溴脱氧尿苷标记显示，这些生长因子增加了心肌细胞和非心肌细胞的DNA合成，但心脏细胞既不显示核分裂也不显示胞质分裂。相反，心肌细胞和nonmyocytes和nonmyocyte-conditioned培养基的共培养未能提高心脏MHC的合成率或其积累，这意味着静止的心脏细胞不响应“空调”的心脏nonmyocytes。这些发现表明，胰岛素和IGFs促进被动加载培养的成年兔心脏细胞肥大，但表明其他生长因子测试可能是有限的，在这方面。
Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.