SEOUL, November 03 (AJP) - So-called forever chemicals can damage human cells from the outside in, starting with the membrane that wraps each cell and reaching the structures that supply its energy, according to a new review from Sookmyung Women’s University.
Per- and polyfluoroalkyl substances (PFAS) are a family of synthetic chemicals that break down so slowly in the environment that they have earned the forever label. The Organisation for Economic Co-operation and Development identified 4,730 PFAS-related substances that may have been on the global market in a 2018 survey.
Studies have linked PFAS to metabolic disorders, developmental toxicity and neurodevelopmental problems. How the chemicals harm cells at the molecular level has remained poorly understood, Sookmyung said.
Kim Hyung-sup, a professor in Sookmyung’s Division of Pharmacy, set out to connect those molecular steps in a paper published in the October issue of Archives of Toxicology, an international toxicology journal.
His starting point was the cell membrane, a thin double layer of fatty molecules called lipids that surrounds every cell. Kim focused on how PFAS act on this layer and change its physical properties.
Those changes matter because the membrane holds two kinds of working proteins. Ion channels are gates that let charged particles such as sodium, potassium and calcium in and out of the cell. Transporters carry specific molecules across. Nerve signals, heartbeats and hormone production all depend on them.
When the membrane shifts, these proteins can malfunction, the review found. In nerve cells, PFAS disturb ion channels and the receptors for neurotransmitters, the chemical messengers neurons use to talk to each other, which changes how readily the cells fire. Kim found PFAS can cause similar faults in ion channels and transporters in the heart and the thyroid.
Transporters play a second role in the story. They also help move PFAS into the body, spread them through tissues and clear them out. That makes them a target of PFAS toxicity and, at the same time, a route that shapes how much of the chemical builds up in the body, Kim explained.
The review then followed the damage more seriously into the cell, to the endoplasmic reticulum, which stores calcium and folds proteins, and to the mitochondria, which produce the cell’s energy. Kim traced how the earlier changes go on to upset the balance of ions inside both.
Earlier research has largely examined these effects one at a time. Kim’s paper links them into a single sequence, running from physical changes in the membrane to faulty membrane proteins to damaged organelles, the university said.
Sookmyung expects the framework to help scientists assess the safety of replacement PFAS, newer compounds with little toxicity data, and to study how other environmental pollutants act on the body.
The paper is a review. It draws together findings from earlier studies rather than reporting new experiments, and Sookmyung described its contribution as groundwork for future research.
The work was funded by the Ministry of Education’s Glocal Lab program and the Ministry of Science and ICT’s basic research program.
[Reference Information]
Journal/Source: Archives of Toxicology (IF 10.9, JCR top 4.7%)
Title: Mechanistic insights into PFAS-induced toxicity: from lipid membrane perturbation to ion channel and transporter dysregulation
DOI: https://bit.ly/4zjW55v
Copyright ⓒ Aju Press All rights reserved.