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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
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Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes
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亚第尼基环酶增加了心肌病的存活率.

David M Roth1, Hamed Bayat, Jeffrey D Drumm

  • 1VA San Diego Healthcare System, San Diego, CA 92161, USA.

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概括
此摘要是机器生成的。

心脏腺环酶VI型 (AC(VI)) 表达量的增加改善了存活率,并在Gq心肌病症中消除了心肌缩. 这项研究表明,AC(VI) 恢复了心脏功能,并增加了受影响小鼠的cAMP生成.

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科学领域:

  • 心血管生物学 心血管生物学
  • 分子心脏病学分子心脏病学
  • 基因工程是一种基因工程.

背景情况:

  • Gq相关心肌病导致心脏cAMP生成的增加.
  • 腺环酶VI型 (AC(VI)) 在心肌病中的生存和缩中的作用尚未完全理解.

研究的目的:

  • 调查心脏AC(VI) 含量增加是否提高了Gq相关心肌病的存活率.
  • 在Gq心肌病的背景下,评估AC(VI) 对心肌缩的影响.

主要方法:

  • 交叉繁殖的小鼠患有Gq相关心肌病症和心脏指导的AC (VI) 表达.
  • 评估Gq/AC,Gq和对照小鼠的存活率,心肌缩 (心室重量/阴茎长度,肌细胞大小),心脏功能 (尺寸,分数缩短) 和cAMP产量.

主要成果:

  • 心脏指导的AC(VI) 表达显著增加了生存率 (P<0.0001).
  • 与Gq小鼠相比,Gq/AC小鼠中的心肌缩和心脏扩张被废除 (P<0.01).
  • Gq/AC小鼠表现出改善的心脏功能,包括减少末端透气直径 (P<0.05) 和增加分数缩短 (P<0.001),增强cAMP产生 (P<0.02).

结论:

  • 心脏指导的AC(VI) 表达恢复了肌细胞的腺基环酶功能.
  • AC(VI) 改善心脏功能,增加cAMP生成,并消除心肌缩.
  • 在Gq心肌病症中,上调AC (VI) 显著增加了存活率.