(Press-News.org) Researchers have for the first time characterised a unique molecular mechanism of the early stages of programmed cell death or apoptosis, a process which plays a crucial role in prevention of cancer.
The study, which is published today (Friday 2nd June 2023) in Science Advances, was led by Dr Luke Clifton at the STFC ISIS Neutron and Muon Source (ISIS) in Oxfordshire, alongside co-lead Professor Gerhard Gröbner at the University of Umeå and partners at the European Spallation Source in Sweden. It is the most recent in a series of research collaborations by this team, investigating the cellular proteins responsible for apoptosis.
Apoptosis is essential for human life, and its disruption can cause cancerous cells to grow and not respond to cancer treatment. In healthy cells, it is regulated by two proteins with opposing roles known as Bax and Bcl-2.
The soluble Bax protein is responsible for the clearance of old or diseased cells, and when activated, it perforates the cell mitochondrial membrane to form pores that trigger programmed cell death. This can be offset by Bcl-2, which is embedded within the mitochondrial membrane, where it acts to prevent untimely cell death by capturing and sequestering Bax proteins.
In cancerous cells, the survival protein Bcl-2 is overproduced, leading to uninhibited cell proliferation. While this process has long since been understood to be important to the development of cancer however, the precise role of Bax and the mitochondrial membrane in apoptosis has been unclear until now.
Dr Luke Clifton, STFC ISIS Neutron and Muon Source scientist and co-lead author, explains: “This work has both advanced our knowledge of fundamental mammalian cell processes and opened exciting possibilities for future research. Understanding what things look like when cells work properly is an important step to understanding what goes wrong in cancerous cells and so this could open doors to possible treatments.”
The team used a technique known as neutron reflectometry (conducted using the advanced ISIS Surf and Offspec instruments) which enabled them to study how Bax interacts with lipids in the mitochondrial membrane. This built on their previous studies of membrane-bound Bcl‑2.
Using neutron reflectometry on SURF and OFFSPEC, they were able to study in real time the way that the protein interacts with lipids present in the mitochondrial membrane, during the initial stages of apoptosis. By employing deuterium-isotope labelling, they determined for the first time that when Bax creates pores, it extracts lipids from the mitochondrial membrane to form lipid-Bax clusters on the mitochondrial surface.
By using time-resolved neutron reflectometry in combination with surface infrared spectroscopy in the ISIS biolab, they were able to see that this pore creation occurred in two stages. Initial fast adsorption of Bax onto the mitochondrial membrane surface was followed by a slower formation of membrane-destroying pores and Bax-lipid clusters, which occurred simultaneously. This slower perforation process occurred on timescales of several hours, comparable to cell death in vivo.
This is the first time that scientists have found direct evidence of the involvement of mitochondrial lipids during membrane perturbing in cell-death initiated by Bax proteins.
Dr Luke Clifton continues: “As far as we can tell, this mechanism by which Bax initiates cell death is previously unseen. Once we know more about the interplay between Bax and Bcl-2 and how it relates to this mechanism, we’ll have a more complete picture of a process that is fundamental to human life. This work really shows the capabilities of neutron reflectometry in structural studies on membrane biochemistry.”
The finding builds on previous studies by the team on the molecular mechanism of membrane-bound Bcl-2 to inform a more complete understanding of the early stages of apoptosis.
Professor Gerhard Gröbner, University of Umeå scientist and and co-lead author says: “The unique findings here will not only have a significant impact in the field of apoptosis research but will also open gateways for exploring Bax and its relatives as interesting targets in cancer therapy such as by tuning up their cell-killing potential.”
Future research is planned at ISIS to further elucidate the molecular mechanism of apoptosis and in particular, to characterise the interplay between Bax and Bcl-2. It is hoped that this will yield insights which will open new avenues of research to continue to develop our understanding of the cellular processes necessary for human life.
END
Scientists reveal new details of cellular process which prevents spread of cancer
2023-06-02
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
Development of an AI-based mass spectrometric technique capable of determining the monomeric sequence of a polymer
2023-06-02
1. The National Institute for Materials Science (NIMS) has developed an AI-based mass spectrometric technique capable of determining the monomeric sequence of a polymer. This technique may be useful in gaining a deeper understanding of basic polymeric structures, facilitating the development of new materials and helping solve plastic recycling problems.
2. A polymer is a very large molecule composed of a chain of many (ranging from hundreds to hundreds of thousands) small molecules called monomers that are bonded together. Many common polymers (e.g., plastics and resins) are copolymers, consisting of several different types of monomers. During the copolymerization process, the monomers ...
Non-invasive treatment of uterine fibroids research project secures grant at Baton Rouge Health-Tech Catalyst Pitch Night
2023-06-02
BATON ROUGE – A collaboration among Dr. Frank Greenway of Pennington Biomedical Research Center, Dr. Beverly Ogden of Woman’s Hospital in partnership with LSU, and the University of Louisiana at Lafayette, was named as one of three award recipients at the Baton Rouge Health-Tech Catalyst Pitch Night. The team will investigate non-invasive treatment of uterine fibroids, or benign growths, such as leiomyomas or myomas, that development from the muscle tissue of the uterus.
“Fibroids are non-cancerous tumors in the wall of the uterus that are common, and can cause bleeding, pain, and infertility,” ...
nTIDE May 2023 Jobs Report: Job numbers rebound bringing people with disabilities close to previous high in employment
2023-06-02
East Hanover, NJ – June 2, 2023 – In a sharp reversal, employment indicators rebounded for people with disabilities in May, according to today’s National Trends in Disability Employment – semi-monthly update (nTIDE), issued by Kessler Foundation and the University of New Hampshire’s Institute on Disability (UNH-IOD). Employment appears to be remaining strong despite the threats to the labor market posed by the debt ceiling crisis and ongoing efforts to control inflation.
Month-to-Month nTIDE Numbers (comparing April 2023 to May 2023)
Based ...
American Tinnitus Association elects Wayne State researcher as new chair
2023-06-02
DETROIT – The American Tinnitus Association (ATA) has elected Jinsheng Zhang, Ph.D., professor and chair of the Department of Communication Sciences and Disorders in Wayne State University’s College of Liberal Arts and Sciences, as the new chair of its board of directors. With decades of experience in tinnitus research and work with the ATA, Zhang aims to assist with proactive recruitment of scientists to the field of tinnitus and engage more researchers in ATA grant opportunities that will spur progress toward more effective treatments and cures.
Tinnitus ...
Media Alert: American College of Cardiology to host Sports Cardiology Conference
2023-06-02
The American College of Cardiology will host the annual Care of the Athletic Heart course on June 8-10, 2023, in Washington, including poster abstracts and educational sessions. The course is designed for all clinicians who provide cardiovascular care for the professional, occupational, tactical or recreational athlete. As the athletic population expands to all demographic groups, it is critical that there is a larger contingent of clinicians who understand the latest care and practice management for athletes at every level.
Dermot Phelan, BAO, MBBCh, PhD, FACC, and Megan Wasfy, ...
Immunotherapy for brain cancer metastases shows clinical benefit
2023-06-02
In a phase 2 clinical trial of the immune checkpoint inhibitor pembrolizumab, investigators found that 42 percent of patients with metastatic brain cancer benefited from the therapy, with seven patients in the trial surviving longer than two years. The authors caution that these benefits must be weighed against risk of toxicity, but, overall, the study shows promising results that warrant larger studies and efforts to identify patients most likely to benefit from this treatment. Their findings are published in Nature Medicine and presented simultaneously at the 2023 ASCO Annual Meeting on June 2.
“There ...
Commentary calls for equal access to healthcare for DACA recipients and all immigrants
2023-06-02
The paper, published April 17 in The Lancet Regional Health – Americas, was co-authored by Dr. Gunisha Kaur, an associate professor of anesthesiology at Weill Cornell Medicine and medical director of the Weill Cornell Center for Human Rights; Stephen Yale-Loehr, a professor of immigration law practice at Cornell Law School; and Jin K. Park, a medical student at the Harvard School of Medicine and the first DACA recipient awarded a Rhodes Scholarship.
“The erratic enforcement of the DACA program since its inception has led many immigrants and their families to disengage completely from the healthcare system to avoid risking deportation,” said ...
Taming a frenzied immune system
2023-06-02
Researchers at the University of Louisville have received $5.8 million in two grants from the National Institutes of Health to expand their work to better understand and prevent immune system dysregulation responsible for acute respiratory distress, the condition responsible for serious illness and death in some COVID-19 patients. A separate $306,000 NIH Small Business Innovation Research grant supports early testing of a compound developed at UofL as a potential treatment.
The three grants combined total $6.1 million.
During the pandemic, health care providers worked tirelessly to treat patients ...
Veterans exposed to Agent Orange may be at increased risk of developing progressive blood cancers
2023-06-02
WASHINGTON --- Research conducted at Georgetown University’s Lombardi Comprehensive Cancer Center and the Washington DC VA Medical Center on a database of veterans exposed to Agent Orange found an association for an increased risk of developing myeloproliferative neoplasms (MPNs), which are acquired stem cell disorders that can lead to overproduction of mature blood cells complicated by an increased risk of blood clots in arteries and veins. When MPNs progress, they can become deadly leukemias.
The findings will be presented at the American Society of Clinical Oncology 2023 annual meeting in Chicago in June.
Agent Orange is an herbicide that was utilized by the United States military ...
Hispanic women still at higher risk for births with neural tube defects after voluntary folic acid fortification of corn masa flour
2023-06-02
The US Food and Drug Administration (FDA) mandated folic acid fortification of all enriched cereal grains in 1996, and this regulation resulted in a reduction of neural tube defect (NTD)–affected pregnancies for the population in the United States. While this mandatory food fortification strategy is an example of a public health success, Hispanic women in the US continued to be twice as likely to give birth to a child affected by NTD compared to non-Hispanic women. It was not until the year 2016 that the FDA approved voluntary, but not mandatory, folic acid fortification for corn masa flour products in the US to focus on the Hispanic diet staples, such ...