Small molecule with a huge potential
Recent findings on the role of IP7, a lesser known molecule, have revealed that it has potential to be developed as a drug for the prevention of stroke and cancer chemotherapy.
ATP molecule is known as a storehouse of energy and fuels the physiological activities. Another equally important but lesser known molecule is IP7, which too carries high energy and regulates many processes in the cell. This molecule consists of a sugar inositol and seven phosphate groups. Its levels in a cell are approximately thousand fold lower than those of ATP.
Studies conducted by scientists at the Centre for DNA Fingerprinting and Diagnostics (CDFD) in Hyderabad have revealed that IP7 plays a crucial role in DNA repair, blood clotting and protein synthesis by ribosomes.
The team led by Dr. Rashna Bhandari, Group Leader, Laboratory of Cell Signalling, CDFD found that mice with lower levels of IP7 show reduced blood clotting. Inadequate levels of IP7 led to reduction in another phosphate-rich molecule called polyphosphate (a long chain of phosphate groups linked to each other).
In mammals, polyphosphate is predominantly found in platelets and helps in strengthening blood clots during their formation. Polyphosphates housed inside platelets break up during clotting. These polyphosphates and other components get released to form a mesh that constitutes the basic structure for clot.
Lowering IP7 levels could have potential applications in the prevention of stroke or myocardial infarction by reducing clotting, said Dr. Rashna.
In their latest work which was published this month in the journal Biochemical Journal, the scientists, using Baker’s yeast, found that the fundamental cellular process of protein synthesis by ribosome was dependent on the levels of IP7 in a cell. “We found that yeast lacking IP7 have a decreased rate of protein synthesis and this process can be reversed if the molecules levels are restored,” she explained.
The scientists found that IP7 transfers one of its phosphates on to a protein that was responsible for the genesis of ribosomes and thereby regulates the process.
In the other study, Dr. Rashna and her team found that cells with lower levels of IP7 were able to trigger a response to DNA damage, but could not complete the repair process. While many of the cells die, a fraction of them continue to divide despite persistent DNA damage and such cells become susceptible to chromosomal abnormalities. “We can reverse these effects by making changes that allow IP7 levels in the cell to be restored,” she added.
“This study highlighted a novel role for IP7 in DNA repair in mammalian cells. Many cancer therapeutics act by causing DNA damage to kill cells. Reducing IP7 levels in a cancer cell might lead to increased cell death and could be one of the ways to supplement cancer chemotherapy,” Dr. Rashna added.
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