失去了心脏的酸3-酶p110α导致收缩功能障碍
Zhongju Lu1, Ya-Ping Jiang, Wei Wang
1Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794-8151, USA.
Circulation
|July 15, 2009
概括
酸3-激酶 (PI3K) p110alpha通过控制L型通道 (LTCCs) 调节心脏收缩性. 失去p110alpha会降低LTCCs,损害心脏功能.
科学领域:
- 心血管生理学心血管生理学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 氨基酸3-酶 (PI3K) p110alpha对于胰岛素作用和癌症至关重要.
- 肌细胞收缩取决于通过L型通道 (LTCCs) 的L型电流 (I(Ca,L)).
研究的目的:
- 调查PI3K p110alpha是否通过调节LTCCs来调节心脏收缩性.
主要方法:
- 在成年老鼠心脏肌细胞中,p110alpha和p110beta的遗传切除.
- 在犬类肌细胞中药理上抑制p110alpha和p110beta.
- 测量I ((Ca,L),LTCC表面表达和心脏功能.
主要成果:
- 在小鼠中,p110alpha的遗传删除,而不是p110beta,降低了I(Ca,L) 和阻断了心脏胰岛素信号传递.
- p110alpha-null肌细胞在细胞表面显示较少的LTCC,导致收缩缺陷和心脏功能减少.
- 药理上抑制p110alpha,但不抑制p110beta,降低了犬类肌细胞中的I,Ca,L和收缩性.
结论:
- PI3K p110alpha,但不是p110beta,是心脏肌细胞中LTCC的关键调节者.
- 减少的p110alpha信号减少了细胞表面的LTCC,减弱了I(Ca,L) 和心脏收缩性.
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