Related Experiment Video
Updated: Aug 11, 2026
Large-Animal Model of Donation after Circulatory Death and Normothermic Regional Perfusion for Cardiac Assessment
Published on: May 10, 2022
Interaction between heat shock protein 70 kDa and calcineurin in cardiovascular systems (Review)
Ashakumary Lakshmikuttyamma1, Ponniah Selvakumar, Rajendra K Sharma
1Department of Pathology, College of Medicine and Health Research Division, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, Canada.
Insights
Heat shock proteins (Hsps) defend cells from stress. This study shows cardiac Hsp70 activates calcineurin (CaN), but phosphorylation by cAMP-dependent protein kinase acts as an on/off switch, offering therapeutic potential for heart diseases.
Area of Science:
- Cellular stress response
- Molecular biology
- Cardiovascular research
Background:
- Heat shock proteins (Hsps) are crucial for cellular defense against stressors.
- Hsps are implicated in cardiovascular diseases like hypertension and atherosclerosis.
- Understanding Hsp interactions is key to developing new therapies.
Purpose of the Study:
- To investigate the interaction between Heat Shock Protein 70 (Hsp70) and calcineurin (CaN).
- To elucidate the regulatory mechanism of CaN signaling by Hsp70.
- To explore the therapeutic implications of Hsp70-CaN interaction in cardiovascular diseases.
Main Methods:
- In vitro experiments to assess Hsp70 and CaN interaction.
- Pull-down assays to confirm direct binding.
- In vitro phosphorylation of Hsp70 by cAMP-dependent protein kinase.
Main Results:
- Cardiac Hsp70 significantly increased calcineurin (CaN) activity (2-fold).
- Hsp70 was shown to directly bind to CaN.
- Phosphorylation of Hsp70 by cAMP-dependent protein kinase inhibited its ability to activate CaN phosphatase activity.
Conclusions:
- Hsp70 directly interacts with and activates CaN.
- Hsp70 phosphorylation by cAMP-dependent protein kinase serves as a regulatory switch for CaN signaling.
- This Hsp70-CaN regulatory mechanism presents a novel therapeutic target for cardiovascular conditions like atherosclerosis and heart failure.
Abstract:
Cells have the capability of defending themselves from various stressors by activating a genetic program with the production of substances known as heat shock proteins (Hsps) and their regulatory partners, the heat shock transcription factors. Hsps play a major role in systemic hypertension, coronary artery disease, carotid atherosclerosis, myocardial infarction and myocardial ischemia. In this review we discuss the interaction between Hsp70 and CaN which was carried out in our laboratory. We demonstrated that the cardiac Hsp70 stimulated a 2-fold increase in calcineurin (CaN) activity. In addition, the pull-down assay revealed that Hsp70 directly interacts with CaN. Furthermore, expressed cardiac specific Hsp70 was phosphorylated in vitro by cAMP-dependent protein kinase. The phosphorylated Hsp70 was unable to activate the phosphatase activity of CaN. For the first time we demonstrated that Hsp70 is phosphorylated by cAMP-dependent protein kinase and provides an on/off switch for the regulation of CaN signaling by Hsp70. This will lead to therapeutic benefit in human diseases such as atherosclerosis, cardiomyopathy, congestive heart failure, and ischemia.
Related Concept Videos
01:16Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
00:51Synthesis and Functions of Calcitonin
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
01:31Regulation of the Unfolded Protein Response
03:00Molecular Chaperones and Protein Folding
The...