Normal cells grow, divide or do any job in response to a set of internal radars that measure energy supply and the environmental factors that tell us what happens outside the cell. Likewise, a protein known as mTOR receives data from the internal and external signals and then allows the cells to take action.
A study conducted by researchers at Johns Hopkins Medicine on mice found a long-sought, built-in molecular switch that can act similar to the car brakes, slowing down the action of mTOR to prevent the heart from enlarging.
The researchers published their findings on January 30 in Nature, the International Journal of Science.
They claim their findings have potential insinuations for manipulating the molecular switch to manage not only heart disease but also other chronic diseases such as diabetes, kidney dysfunction, lung disease, cancer, and autoimmune disorders.
The term mTOR derives from an immunosuppressive drug called Rapamycin, which is predominantly recommended to prevent transplanted organ rejection. The drug is also used to treat genetic diseases and some rare cancers.
The senior study author, David Kass, said, “The problem with the few drugs that we have to manipulate mTORC1 is that they are essentially turning it off, which also shuts down its normal function in the cells.” “That means if you use it to, say, treat a tumor, you suppress the immune system as well, and might cause diabetes, or kidney and other organ damage by blocking mTORC1 in the other cells.”
Mark Ranek, lead author, who has been working in Kass’ laboratory, was studying how this other protein known as Protein Kinase G protected heart tissue from damage and disease. He surprisingly discovered that turning on protein kinase G stopped mTOR. He then figured out how exactly this happens.
He says the answer lies in a key regulator of mTORC1 known as tuberin that acts like an “antenna” for biochemical signals, blocking cell growth and regulating metabolism. Protein Kinase G is also one of the targets of a prescription drug called sildenafil citrate, which is sold under the brand name Viagra.
Ranek said, “Instead of turning mTORC1 off, we had something that looked more like a car brake, which was effective only if the car (mTORC1) was on and active.”
The team altered human tuberin protein in some places that were altered by Protein Kinase G with the help of genetic engineering tools in heart muscle and connective tissue cells.
Kass said, “The process would require some type of gene therapy, which means putting the gene into a virus that then transfers it to the heart.” “However, the tuberin gene is too big to fit into viruses we currently have for this job.”
The drugs that activate Protein Kinase G – such as nitroglycerin and sildenafil citrate – are used to relax blood vessels in patients with pulmonary hypertension, coronary artery disease, and erectile dysfunction. The study shows how the drugs may be useful in heart diseases in which mTORC1 is active. Because of the promising results, many authors have formed a company to discover and understand further developments of immune system controllers.
