Wei-Zhong Zhu, Shi-Qiang Wang, Khalid Chakir, Dongmei Yang, Tong Zhang, Joan Heller Brown, Eric Devic, Brian K. Kobilka, Heping Cheng, Rui-Ping Xiao
J Clin Invest.
2003;
111(5):617–625
doi:10.1172/JCI16326
This article Copyright © 2003, The American Society for Clinical Investigation
Abstract
|
Full text
|
PDF
&
#x003b2;1-adrenergic receptor (β1AR) stimulation activates the classic cAMP/protein kinase A (PKA) pathway to regulate vital cellular processes from the change of gene expression to the control of metabolism, muscle contraction, and cell apoptosis. Here we show that sustained β1AR stimulation promotes cardiac myocyte apoptosis by activation of Ca2+/calmodulin kinase II (CaMKII), independently of PKA signaling. β1AR-induced apoptosis is resistant to inhibition of PKA by a specific peptide inhibitor, PKI14-22, or an inactive cAMP analogue, Rp-8-CPT-cAMPS. In contrast, the β1AR proapoptotic effect is associated with non–PKA-dependent increases in intracellular Ca2+ and CaMKII activity. Blocking the L-type Ca2+ channel, buffering intracellular Ca2+, or inhibiting CaMKII activity fully protects cardiac myocytes against β1AR-induced apoptosis, and overexpressing a cardiac CaMKII isoform, CaMKII-δC, markedly exaggerates the β1AR apoptotic effect. These findings indicate that CaMKII constitutes a novel PKA-independent linkage of β1AR stimulation to cardiomyocyte apoptosis that has been implicated in the overall process of chronic heart failure.
This file is in Adobe Acrobat (PDF) format.
If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not
allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users:
Right-click on the Download link and choose the option that says something like "Save Link As...".
Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you
configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can
usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
