About Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Biochemical Pathway That Protects Cells from Cell Death Identified

by Colleen Fleiss on January 16, 2021 at 8:46 PM
Font : A-A+

Biochemical Pathway That Protects Cells from Cell Death Identified

A newly identified biochemical pathway protects cells from a type of cell death called ferroptosis, said Moffitt Cancer Center researchers. The findings of the study are published in Cell Metabolism.

The hallmarks of cancer include rapid cell reproduction and metabolic activity. But these processes also lead to increased cellular stress and oxidation, and the risk of cell death.

Advertisement


Ferroptosis is a specialized type of cell death that is caused by imbalances in oxidation within cells. Ferroptosis results in changes to molecules in the cell membrane called lipids and can be caused by cysteine starvation.

Cysteine is a type of amino acid that is one of the building blocks of proteins and is also used by the body for numerous important physiological processes, including cell survival, regulation of oxidative-reduction reactions and energy transfer.
Advertisement

Because of its critical role in normal processes, cysteine is highly regulated to prevent excess or insufficient amounts of the amino acid.

Several different types of cancer overexpress molecules that play an important role in cysteine regulation. This suggests that reducing cysteine levels may negatively affect cancer growth.

In fact, studies have shown that cancer cells can be induced to undergo cell death by either inhibiting cysteine uptake or starving cells of cysteine.

However, the downstream processes that are stimulated by cysteine starvation are unclear. Moffitt researchers performed a series of laboratory investigations to learn what molecules become activated after cysteine deprivation and how this impacts cells.

The researchers discovered that cancer cells can activate signaling pathways to protect themselves against cell death due to cysteine starvation.

When the team starved non-small cell lung carcinoma cells of cysteine, the cells began to undergo ferroptosis. However, cysteine starvation also resulted in an unexpected accumulation of small molecules called γ-glutamyl-peptides, which protected the cells against ferroptosis.

The researchers found that the peptides were synthesized through the activity of the protein GCLC. Under normal conditions, GCLC is involved in the first step of the synthesis of the antioxidant glutathione from the amino acids cysteine and glutamate.

However, this newly discovered activity of GCLC occurred in the absence of cysteine and was important to limit both glutamate accumulation and oxidant production.

The researchers further analyzed signaling mechanisms controlling GCLC-mediated peptide synthesis and discovered that GCLC was regulated by the protein NRF2.

They found that under normal conditions, NRF2 regulated GCLC to produce glutathione, but under cysteine-starved conditions, NRF2 regulated GGLC to produce γ-glutamyl-peptides.

"NRF2 is known to play an important role in the protection against cellular oxidation and is often deregulated in lung cancer," said lead author Gina DeNicola, Ph.D., assistant member of the Cancer Physiology Department at Moffitt.

"The ability of NRF2 to protect against ferroptosis has important implications for cancer, particularly lung cancers that commonly have NRF2 activation via mutations in KEAP1 and NRF2."

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
What's New on Medindia
Monkeypox Outbreak: What it is, How Does it Spread & the Prevention
Seasonal Allergy Medications
How to Choose the Best Eczema-Friendly Moisturizer for Children?
View all
Recommended Reading
News Archive
Date
Category
News Category

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Parkinsons Disease Surgical Treatment Death Facts Bereavement Autophagy: Self-Repair Mechanism at Cellular Level 

Most Popular on Medindia

How to Reduce School Bag Weight - Simple Tips Blood Pressure Calculator Find a Hospital Blood Donation - Recipients Turmeric Powder - Health Benefits, Uses & Side Effects Selfie Addiction Calculator Sinopril (2mg) (Lacidipine) Indian Medical Journals Sanatogen Drug Interaction Checker

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2022

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use
open close
ASK A DOCTOR ONLINE