Tuesday, April 26, 2011

Vote Troponin for Protein of the Year!

Vote Troponin for Protein of the Year!

Troponin is a wonderful protein that allows for skeletal muscle and cardiac muscle contraction. I don’t know about you but I think that the heart is a pretty important organ. Without this protein, our hearts would not beat and we would die. End of story. But thanks to troponin, our hearts can function as well as our skeletal muscle. Personally being able to move is a pretty great thing. I wouldn’t be able to make peptides and run the NMR if I couldn’t use my hands or eyes. So let’s explore a little bit more about this amazing protein…

First of all troponin is comprised of three subunits of troponin, troponin C, I and T. Calcium activates the troponin complex by binding to a subunit. The binding of calcium induces a conformational change in one subunit. That subunit then causes a conformational change in the second subunit and the second causes a conformational change in the third subunit. Troponin C is the site at which the calcium binds. Troponin I bind to actin and troponin T binds to tropomyosin. Troponin T anchors the protein complex onto the actin. This is a very ordered structure. Only God could have designed something so amazing!

The top part of the diagram shows the muscle fiber without calcium bound and the bottom part shows the muscle fiber when calcium is bound.

Lots of studies have been done with troponin and cardiac muscle. Research has shown that levels of troponin in cardiac tissue can be used to determine if patients are at risk of developing coronary artery disease or graft failure when tissue transplant is performed. This is useful information that could make tissue transplants easier. Heart failure results from decreased sensitization of troponin to Ca2+. Research is being done to find sensitizing agents that can increase the sensitivity of troponin to Ca2+ thus stopping heart failure. This would be a great medical advancement. As you can see, troponin has lots of potential in the medical field. And these are just a few of the many reasons that troponin should be the protein of the year!

Labarrere, MD, Carlos A., David R. Nelson, MS, Catherine J. Cox, MD, Douglus Pitts MD, and Philip Kirlin MD. "Cardiac-Specific Troponin I Levels and Risk of Coronary Artery Disease and Graft Failure Following Heart Transplantation." JAMA 284.426 July (2000). Web. 26 Apr. 2011.

Wen-Ji, Dong, Jianli An, Jun Xing, and Herbert Cheung. "Structural transition of the inhibitory region of troponin I within the regulated cardiac thin filament." Arch Biochem Biophys 45615 Dec. (2006): 135-42. Web. 26 Apr. 2011.

Kleerekoper, Qiunn, and John A. Putkey. "Drug Binding to Cardiac Troponin C*." Journal of Biological Chemistry 274.3420 Aug. (1999). Web. 26 Apr. 2011.

Monday, March 14, 2011

Troponin T and I have been used to study myocardial cell damage due to angina and myocardial infarction. Angina is a condition in which there are sharp chest pains, usually associated with blocked arteries. Troponin T and I have also been used to study the effects transplant rejection, after a heart transplant surgery. Transplant rejection occurs when the new tissues are not accepted by the body’s own tissues and the new tissues are attacked. It is thought that rejection should lead to elevated levels of troponin. This experiment was designed to test whether cell damage due to rejection could be detected based on the levels of troponin. This would be important to determine if there is persistent damage to the cells. The researchers showed that there were indeed elevated levels of troponin to indicate cell damage. This information could be useful in determining how to decrease the risk of rejection of tissues when transplants occur


Structure of the Troponin Complex and Heart Diseases

Cardiovascular disease is the number one cause of death in the United States. Death occurs due to the inability of the heart to distribute blood to the body. This is in turn caused by the inability of the heart of contract. The contraction of the heart is caused by troponin. In this experiment, the researchers were testing the effect that green tea has on the heart and the ability of troponin to bind Ca2+. Troponin is a complex made up of two polymers. There is a backbone that is made up of a double helix of actin. On consecutive actin molecules, there is a trimer of troponin C, I and T. Troponin c is the site at which the Ca2+ binds. Troponin I is the inhibitory unit of the complex, it serves to regulate the actin-myosin bridge. Troponin T anchors the complex to the filament.  
In this experiment, it was found that drugs that alter the sensitivity of the troponin complex to Ca2+ is a safer route than altering the cystolic concentration of Ca2+. An increase in sensitivity could increase the amount of Ca that binds to troponin and this causes the heart to contract. Also desensitizers could protect the heart against hypertrophic cardiomyopathy, which is enlargement of the heart. The desensitizers would make the Ca less likely to bind to the troponin and cause an increase in the rate of heart contractions. These sensitizers do not inhibit Ca concentrations, therefore they do not affect homeostasis.


Troponin and the Heart

Troponin is a protein that is present in muscle. It is central to muscle contraction. When calcium channels open, the calcium binds to the troponin, causing a conformational change. This change opens a space that allows actin to bind and begin muscle contraction. Troponin is a component of skeletal and cardiac muscle. Troponin has been used in much research with regard to the heart. In this particular article, the researchers were experimenting with Ca2+ sensitizing agents. Cognitive heart failure results when there is desensitization of the heart muscle to Ca2+. Ca2+ channels are what cause the change in troponin to cause muscle contraction. Ideal sensitizers are compounds that would increase the flux of ions in the channel and create a powerful muscle contraction. Troponin C, one of three types of troponin, is the critical to muscle contraction in the heart. Without this protein, the heart would not be able to contract and blood would fail to be pumped to the body and death would result. This protein is crucial for the beating of the heart. (lub dub)