Contact Information:

Media Contact

Bonnie Ward
bjward@ucsd.edu
619-543-6163

Twitter: UCSanDiego

http://www.ucsd.edu




Kredyty mieszkaniowe Kredyty mieszkaniowe

Sprawdź aktualny ranking najlepszych kredytów mieszkaniowych w Polsce - atrakcyjne kredytowanie nieruchomości.
PRESS-NEWS.org - Press Release Distribution
FREE PRESS RELEASES DISTRIBUTION
RSS - Press News Release
Add Press Release

Control switch that modulates cell stress response may be key to multiple diseases


2015-03-25
(Press-News.org) Researchers at the University of California, San Diego School of Medicine have discovered a control switch for the unfolded protein response (UPR), a cellular stress relief mechanism drawing major scientific interest because of its role in cancer, diabetes, inflammatory disorders and several neural degenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), otherwise known as Lou Gehrig's disease.

The normal function of the UPR pathway is to protect cells from stress but it can also trigger their death if the stress is not resolved. The researchers' discovery of a control switch that acts on the UPR pathway, published March 25 in the online edition of EMBO Reports, opens new drug development avenues for treating a wide variety of diseases by modulating the UPR pathway to prevent excessive cell death.

"Our paper reports that two highly conserved pathways - the UPR and the nonsense-mediated RNA decay pathway - intersect with each other at a pivotal point in cell stress," said Miles Wilkinson, PhD, senior author and professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine. "In essence, we've shown that the nonsense-mediated RNA decay pathway, typically referred to as 'NMD,' keeps the UPR in check to avoid the potentially dangerous consequences if the UPR pathway were allowed to mount an inadvertent response to innocuous stress."

In cells, like people, too much stress can cause bad things to happen. In the case of cells, one such bad consequence is the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), the cell's protein-making factory. To carry out their many biological functions, proteins must be precisely folded in the correct shape. The body's answer to excessive cell stress and accompanying misshapen proteins is the unfolded protein response. The UPR kicks in and restores normal ER-folding capacity by adjusting certain cellular processes. If this fails, the UPR instructs the cell to self-destruct, a process known as programmed cell death or apoptosis.

Wilkinson describes the UPR pathway as a double-edged sword. "In a large number of diseases, ranging from cancer to ALS, major stress occurs in the affected cells, leading the UPR pathway to be triggered," he said. "And that's meant to be helpful. But if the stress isn't relieved in a timely fashion, it triggers cell death. A limited amount of cell death is normal, but if too many cells die, especially critical cells, then it's a problem. Chronic UPR activation and excessive cell death has been implicated in brain disorders like Alzheimer's and Parkinson's disease."

In their study, Wilkinson, with first author Rachid Karam, PhD, and colleagues found that the NMD pathway plays a critical role in shaping the activities of UPR. Specifically, they discovered that NMD prevents inappropriate activation of the UPR and also promotes its timely termination to protect cells from prolonged ER stress. "Because of the important role of UPR in regulating cell life/death decisions, it is critical that mechanisms are in place to prevent unnecessary UPR activation in response to innocuous or low-level stimuli," said Wilkinson. "In this report we demonstrate that the NMD pathway serves in this capacity by raising the threshold for triggering UPR and also promoting its shut off at the appropriate time."

He added that NMD doesn't deter the UPR if an important stress comes along where more action is needed. "Although NMD normally represses the UPR, our paper and previous work have shown that it gets out of the way if there's a real problem," Wilkinson noted.

Previous studies from the Wilkinson group and others have established that NMD has two broad roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA) - molecules that are essential for transcribing genetic information into the construction of proteins critical for life. Second, NMD degrades a specific group of normal mRNAs.

The latest study shows that NMD suppresses inappropriate UPR activities by driving the rapid decay of several normal mRNAs encoding proteins critical for the UPR. "We demonstrate that NMD directly targets the mRNAs encoding several UPR components, including the highly conserved UPR sensor, IRE1-alpha, whose NMD-dependent degradation partly underpins this process," said Wilkinson. "Our work not only sheds light on UPR regulation, but demonstrates the physiological relevance of NMD's ability to regulate normal mRNAs."

INFORMATION:

Co-authors include Chih-Hong Lou, Heike Kroeger, Jonathan H. Lin, all at UC San Diego; Lulu Huang, formerly of UC San Diego and now at ISIS Pharmaceuticals.

Funding for this research came, in part, from NIH grant (RO1 GM111838).


ELSE PRESS RELEASES FROM THIS DATE:

Team discovers link between lifestyles of indigenous communities & gut microbial ecologies

2015-03-25
An international team of researchers led by the University of Oklahoma has discovered a strong association between the lifestyles of indigenous communities and their gut microbial ecologies (gut microbiome), a study that may have implications for the health of all people. Under the direction of Cecil Lewis, co-director of the Laboratories of Molecular Anthropology and Microbiome Research in the OU College of Arts and Sciences, the team presents an in-depth analysis of the gut microbiome of the Matses, an Amazonian hunter-gatherer community, which is compared with that ...

The Lancet: Phase 1 trial of first Ebola vaccine based on 2014 virus strain shows vaccine is safe and provokes an immune response

2015-03-25
Results from the first phase 1 trial of an Ebola vaccine based on the current (2014) strain of the virus are today published in The Lancet. Until now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. The results suggest that the new vaccine is safe, and provokes an immune response in recipients, although further long-term testing will be needed to establish whether it can protect against the Ebola virus. A team of researchers, led by Professor Fengcai Zhu, from the Jiangsu provincial center for disease prevention and ...

Head injury patients show signs of faster aging in the brain

2015-03-25
People who have suffered serious head injuries show changes in brain structure resembling those seen in older people, according to a new study. Researchers at Imperial College London analysed brain scans from over 1,500 healthy people to develop a computer program that could predict a person's age from their brain scan. Then they used the program to estimate the "brain age" of 113 more healthy people and 99 patients who had suffered traumatic brain injuries. The brain injury patients were estimated to be around five years older on average than their real age. Head ...

Global Oncology launches Global Cancer Project Map for cancer research access with NCI

2015-03-25
Boston, Mass. - March 25, 2015 - Nonprofit Global Oncology, Inc. (GO) today announced the launch of the Global Cancer Project Map, a first-of-its-kind online resource and virtual information exchange for connecting the global cancer community. Developed by GO in collaboration with the National Cancer Institute (NCI) Center for Global Health, the Map enables worldwide access to cancer projects and expertise to improve cancer practices and patient outcomes, especially in low-resource settings. Find the Global Cancer Project Map here: http://gcpm.globalonc.org. The Map was ...

Greenhouse gases unbalanced

2015-03-25
25.03.2015: Natural wetlands usually emit methane and sequester carbon dioxide. Anthropogenic interventions, in particular the conversion of wetlands for agriculture, result in a significant increase in CO2 emissions, which overcompensate potential decreases in methane emission. A large international research team now calculated that the conversion of arctic and boreal wetlands into agricultural land would result in an additional cumulative radiative forcing of about 0,1 MilliJoule (mJ) per square meter for the next 100 years. The conversion of temperate wetlands into agricultural ...

Hospitals and physicians should improve communication for better patient care

2015-03-25
AURORA, Colo. (March 25, 2015) - Coordinating patient care between hospital clinicians and primary-care physicians is a significant challenge due to poor communication and gaps in information-sharing strategies, according to a study led by physicians at the School of Medicine of the University of Colorado Anschutz Medical Campus. The inability to share timely information can increase the risk of missed test results and hospital readmissions, according to the study's corresponding author, Christine D. Jones, MD, assistant professor of medicine and director of the Hospital ...

Researchers find promising new biomarkers for concussion

2015-03-25
PROVIDENCE, R.I. [Brown University] -- By looking at the molecular aftermath of concussion in an unusual way, a team of researchers at Brown University and the Lifespan health system has developed a candidate panel of blood biomarkers that can accurately signal mild traumatic brain injury within hours using standard, widely available lab arrays. The results appear in a new study in the Journal of Neurotrauma. Many researchers have reported recent progress in identifying possible blood biomarkers for concussion -- an advance sought because diagnosis is currently limited ...

Singapore identifies mutations that may enable earlier diagnosis of colorectal cancer recurrence

2015-03-25
Singapore, 18 March 2015- A multi-disciplinary team of doctors and scientists from Singapore has characterised the genetic changes associated with the spread of colorectal cancer to the liver. This finding is significant in helping to develop personalised diagnostic tests for patients with colorectal cancer based on the genetic changes present in each individual's colon tumour. The research team comprises representatives from National Cancer Centre Singapore (NCCS), Singapore General Hospital (SGH), Duke-NUS Graduate Medical School (Duke-NUS), A*STAR's Genome Institute ...

Perceived open-mindedness explains religion-based dating

2015-03-25
Across a number of faiths and cultures, people tend to date and marry others who share their religious beliefs. Now, new psychology research from New Zealand's University of Otago suggests this phenomenon--known as 'religious homogamy'--is partially a result of inferences about religious people's personalities. The researchers measured how religious and non-religious individuals perceive the 'openness'--a primary dimension of personality associated with intellectual curiosity--of potential religious and non-religious mates. They found that non-religious participants in ...

Pregnant women not getting enough omega-3, critical for infant development

2015-03-25
This news release is available in French. Alberta Pregnancy Outcomes and Nutrition (APrON) is a birth cohort involving over two thousand women and their infants from Calgary and Edmonton that was funded by Alberta Innovates Health Solutions and includes researchers at the University of Alberta and the University of Calgary. The main objective of APrON is to understand the relationship between maternal nutrient status during pregnancy and maternal mental health and child health and development. As part of the project, the APrON team studied the first 600 women in the ...

LAST 30 PRESS RELEASES:

How your brain decides blame and punishment -- and how it can be changed

Uniquely human brain region enables punishment decisions

Pinpointing punishment

Chapman University publishes research on attractiveness and mating

E-cigarettes: Special issue from Nicotine & Tobacco Research

Placental problems in early pregnancy associated with 5-fold increased risk of OB & fetal disorders

UT study: Invasive brood parasites a threat to native bird species

Criminals acquire guns through social connections

Restoring ocean health

Report: Cancer remains leading cause of death in US Hispanics

Twin study suggests genetic factors contribute to insomnia in adults

To be fragrant or not: Why do some male hairstreak butterflies lack scent organs?

International team discovers natural defense against HIV

Bolivian biodiversity observatory takes its first steps

Choice of college major influences lifetime earnings more than simply getting a degree

Dominant strain of drug-resistant MRSA decreases in hospitals, but persists in community

Synthetic biology needs robust safety mechanisms before real world application

US defense agencies increase investment in federal synthetic biology research

Robots help to map England's only deep-water Marine Conservation Zone

Mayo researchers identify protein -- may predict who will respond to PD-1 immunotherapy for melanoma

How much water do US fracking operations really use?

New approach to mammograms could improve reliability

The influence of citizen science grows despite some resistance

Unlocking secrets of how fossils form

What happens on the molecular level when smog gets into the lungs?

Using ultrasound to clean medical instruments

Platinum and iron oxide working together get the job done

Tiny silica particles could be used to repair damaged teeth, research shows

A quantum lab for everyone

No way? Charity's logo may influence perception of food in package

[Press-News.org] Control switch that modulates cell stress response may be key to multiple diseases
Press-News.org is a service of DragonFly Company. All Rights Reserved.
Issuers of news releases are solely responsible for the accuracy of their content.