阿尔法和β上腺素通路在老鼠心肌细胞中差异调节细胞类型特定的细胞亡
E Iwai-Kanai1, K Hasegawa, M Araki
1Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Circulation
|July 21, 1999
概括
阿尔法和β上腺素路径差异调节心脏肌细胞亡. β-上腺素刺激通过cAMP-蛋白激酶A诱导了亡,而α-上腺素刺激则抑制了亡.
科学领域:
- 心血管生物学 心血管生物学
- 细胞信号传输 细胞信号传输
- 细胞亡研究研究
背景情况:
- 心脏肌细胞亡与心力衰竭的发展有关.
- 上腺素在心力衰竭中被激活,可以诱导心肌细胞亡.
- 阿尔法和β上腺素通路在调节亡中的独特作用仍然不清楚.
研究的目的:
- 调查alpha和beta-adrenergic通路是否协调或差异调节心肌细胞亡.
- 为了确定细胞亡途径是否涉及到常见的或细胞类型特定的信号.
主要方法:
- 培养的新生小鼠心肌细胞被刺激使用α-1-上腺体激动剂 (乙烯),β-上腺体激动剂 (异二醇) 或cAMP模拟物 (8-Br-cAMP).
- 通过TUNEL染色和DNA碎片化来评估亡.
- 用蛋白质激酶A,α(1) - 上腺素受体和MEK-1的抑制剂来阐明信号通路.
主要成果:
- β-上腺素刺激 (异二醇) 和cAMP类似物显著增加了心脏肌细胞亡.
- 异二醇诱导的亡被蛋白质激酶A抑制剂抑制.
- 1-上腺激素刺激 (乙烯) 抑制了cAMP模拟物诱导的亡,这种效应被普拉佐辛和MEK-1抑制剂阻断.
- 该cAMP模拟物诱导心脏肌细胞的亡,但阻断了PC12细胞的亡.
结论:
- 阿尔法和β上腺素通路对心肌细胞亡产生差异性调节.
- 一个cAMP-蛋白激酶A通路对于β-上腺激素激活剂诱导的亡是必不可少的.
- 这种特定的亡途径似乎在其他细胞类型 (如PC12细胞) 中是非功能性的.
相关概念视频
01:31Adrenergic Receptors: ɑ Subtype
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
01:26Adrenergic Receptors: β Subtype
β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...