New
Delhi : Indian scientists have found a new fuction of a gene which is aleady
known to play a role in neurological disorders.
Scientists
at the Indian Institute of Science Education and Research (IISER) Pune
have found that the gene, ABHD12, is involved in mitigating
oxidative stress-induced cell death in brain cells by breaking down oxidized state
of a lipid, phosphatidylserine, found in cell membrane.
Given
the known function of this gene in neurological disorders, the new
finding indicates plausible connections between oxidative stress and
neurological disorders, according to results published in journal Nature
Chemical Biology.
A
cell has a finite lifetime and it is driven to
death when there is overproduction of reactive oxygen species (ROS) leading
to oxidative stress. ROS is a byproduct of the functioning
of mitochondria – powerhouse of the cell. ROS damages
lipid membranes or boundary of the cell, DNA as well as proteins of the cell.
Earlier
studies have shown that phosphatidylserine, a class of lipids found in the
cell membrane, when oxidized by ROS, flip
their direction from inner of the cell to
the outside which triggers cell death.
IISER
study has revealed that ABHD12, a
gene encoding serine hydrolase lipase, can breakdown the oxidized form of lipid phosphatidylserine, preventing the cell from
death.
“Mutation
in ABHD12 results in a human neurological disorder called PHARC (acronym for polyneuropathy, hearing loss,
ataxia, retinitis pigmentosa and cataract). Our findings will enable study of PHARC,
progression of disease pathology and
possibly develop new therapeutic interventions towards the treatment of this
early onset disorder,” said Dr. Siddhesh Kamat, leader of the research team, while
talking to India Science Wire.
For
this study, scientists first synthesized a chemical moiety which could release
ROS in cultured mammalian cells, thus mimicking oxidative stress environment in
the cell. After administering this ROS stress, scientists measured oxidized PS
levels. To get lipase enzyme that metabolizes
the oxidized PS, scientists used various lipase inhibitors and found that three
inhibitors whose application increases the oxidized PS in the cell. Proteome
analysis helped researchers conclude that a lipase encoded by the gene ABHD12
mitigates cell death by breaking down oxidized PS.
The
research team led by Dr. Siddhesh Kamat included Dhanashree S. Kelkar, Neelay Mehendale, Shubham Singh and Alaumy Joshi ,
Amol Mhetre, Abinaya Rajendran, Govindan Ravikumar, Ajay Kumar Sharma and
Harinath Chakrapani.
By Dr. Aditi Jain
(India Science Wire)
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