PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Study IDs key protein for cell death

2013-05-15
(Press-News.org) CAMBRIDGE, MA -- When cells suffer too much DNA damage, they are usually forced to undergo programmed cell death, or apoptosis. However, cancer cells often ignore these signals, flourishing even after chemotherapy drugs have ravaged their DNA.

A new finding from MIT researchers may offer a way to overcome that resistance: The team has identified a key protein involved in an alternative death pathway known as programmed necrosis. Drugs that mimic the effects of this protein could push cancer cells that are resistant to apoptosis into necrosis instead.

While apoptosis is a tightly controlled procedure that breaks down and disposes of the dying cell in a very orderly way, necrosis is a messier process in which the cell's membrane ruptures and its contents spill out.

"People really used to think of necrosis as cells just falling apart, that it wasn't programmed and didn't require gene products to make it happen," says Leona Samson, a member of MIT's Center for Environmental Health Sciences and Koch Institute for Integrative Cancer Research. "In the last few years it has become more clear that this is an active process that requires proteins to take place."

In the May 10 online edition of the journal Genes and Development, Samson and colleagues report that a protein known as ALKBH7 plays a key role in controlling the programmed necrosis pathway. Dragony Fu, a former postdoc in Samson's lab, is the paper's lead author, and postdoc Jennifer Jordan is also an author.

Unexpected findings

ALKBH7 belongs to a family of proteins first discovered in E. coli about a dozen years ago as part of a DNA-repair mechanism. In humans, there are nine different ALKBH proteins, which Samson's lab has been studying for several years.

Most of the mammalian ALKBH proteins appear to be involved in DNA repair, similar to the original E. coli version. In particular, they respond to DNA damage caused by alkylating agents. These agents can be found in pollutants such as fuel exhaust and tobacco smoke, and are also used to treat cancer.

In the new paper, Samson, a professor of biology and biological engineering, and her colleagues found that ALKBH7 has an unexpected effect. When the researchers lowered ALKBH7 levels in human cells grown in the lab, those cells were much more likely to survive DNA damage than cells with normal ALKBH7 levels. This suggests that ALKBH7 actually promotes cell death.

"That was a surprising finding, because previously all of these ALKBH proteins were shown to be helping the cell survive when exposed to damage," says Fu, who is now a visiting research fellow at the University of Zurich.

Upon further investigation, the researchers found that when healthy cells suffer massive DNA damage from alkylating agents, they enter the programmed necrosis pathway. Necrosis, which can also be initiated by bacterial or viral infection, is believed to help the body's immune system detect threats.

"When dying cells release their contents during necrosis, it serves as a warning signal for your body that there is a virus there and recruits macrophages and other immune cells to the area," Fu says.

Potential drug targets

The findings suggest that when DNA is so badly harmed that cells can't repair it, the programmed necrosis pathway kicks in to prevent cells with major genetic damage from potentially become cancerous.

Other researchers have shown that some types of cancer cells have much lower ALKBH7 levels than normal cells. This suggests that the cancer cells have gained the ability to evade programmed necrosis, helping them to survive, Fu says.

The necrosis pathway appears to be initiated by an enzyme called PARP, which becomes hyperactive following DNA damage and shuts down the cell's production of two molecules that carry energy, ATP and NAD. The MIT team found that ALKBH7 prevents ATP and NAD levels from returning to normal by disrupting the function of mitochondria — the cell structures that generate energy for a cell.

Without an adequate supply of those critical energy-carrying molecules, the cell cannot survive and undergoes necrosis. In cells that lack ALKBH7, ATP and NAD levels rebound, and the cells survive, carrying a heavy burden of DNA damage.

The researchers are now investigating the molecular details of the programmed necrosis pathway in hopes of identifying ways to activate it in cancer cells. ### The research was funded by the National Institutes of Health and the American Cancer Society.

Written by Anne Trafton, MIT News Office


ELSE PRESS RELEASES FROM THIS DATE:

Massage therapy shown to improve stress response in preterm infants

2013-05-15
LOUISVILLE, Ky. – It seems that even for the smallest of people, a gentle massage may be beneficial. Newborn intensive care units (NICUs) are stressful environments for preterm infants; mechanical ventilation, medical procedures, caregiving activities and maternal separation create these stressful conditions. Born under-developed, preemies have an immature autonomic nervous system (ANS), which controls stress response and recovery. For a preemie, even a diaper change is stressful and the immature ANS over reacts to these stressors. Since preterm infants can't process ...

UC Riverside scientists discovering new uses for tiny carbon nanotubes

2013-05-15
RIVERSIDE, Calif. (http://www.ucr.edu)— The atom-sized world of carbon nanotubes holds great promise for a future demanding smaller and faster electronic components. Nanotubes are stronger than steel and smaller than any element of silicon-based electronics—the ubiquitous component of today's electrical devices—and have better conductivity, which means they can potentially process information faster while using less energy. The challenge has been figuring out how to incorporate all those great properties into useful electronic devices. A new discovery by four scientists ...

Evidence of host adaptation of avian-origin influenza A virus

2013-05-15
A novel avian-origin reassortant influenza A (H7N9) virus emerged in China in February 2013, and is associated with severe lower respiratory tract diseases. To date, more than 100 human cases of infection, including at least 20 deaths, have been reported in China. Three early cases of infection were described in Hangzhou, Zhejiang Province, China. The general clinical features of the three patients were similar to the previously reported cases in China. Two of the three patients had a history of direct contact with live poultry markets. Interestingly, poultry cage swabs ...

New blood test finds allergies before implant surgery

2013-05-15
Imagine what Paula Spurlock must have been going through. Shortly after having a hip replaced in 2011, the trouble started. "I had horrible itching, really bad migraines and intense pain throughout my body," she said. "I couldn't take it. Every single thing in me itched." After many months and several trips to specialists, Spurlock was told it could be anything from food allergies to her medication. But no matter what she changed, the symptoms persisted and Spurlock resigned herself to a life of misery. "I just kind of thought that's what life was going to be like," ...

Novel study reports marijuana users have better blood sugar control

2013-05-15
Philadelphia, PA, May 15, 2013 – Regular marijuana use is associated with favorable indices related to diabetic control, say investigators. They found that current marijuana users had significantly lower fasting insulin and were less likely to be insulin resistant, even after excluding patients with a diagnosis of diabetes mellitus. Their findings are reported in the current issue of The American Journal of Medicine. Marijuana (Cannabis sativa) has been used for centuries to relieve pain, improve mood, and increase appetite. Outlawed in the United States in 1937, its ...

Why and when a stepparent may adopt a stepchild in South Carolina

2013-05-15
Why and when a stepparent may adopt a stepchild in South Carolina Article provided by Williams Hendrix Steigner & Brink, P.A. Visit us at http://www.whsblawfirm.com These days, it's not at all uncommon for a husband or a wife to bring children from a previous relationship into a marriage. When two households combine in such a fashion, a strong emotional bond often develops between the stepparent and stepchild. Yet, however close a stepparent is to his or her stepchildren, legally speaking, stepparents may not be entitled to all the same rights as biological ...

More Americans losing loved ones to car crashes as traffic deaths rise

2013-05-15
More Americans losing loved ones to car crashes as traffic deaths rise Article provided by Smith Magram Berenato Michaud P.C. Visit us at http://www.injurylawyernj.com/ For most of the last decade, the United States has made great strides in reducing deaths and injuries from car accidents. But, in May of 2013, the National Highway Traffic Safety Administration released an official estimate of last year's motor vehicle death total, and it appears the United States has lost some momentum in terms of traffic safety. More miles traveled, increased motorcycle use ...

Show the State the money: What happens when you die without a will in Ohio?

2013-05-15
Show the State the money: What happens when you die without a will in Ohio? Article provided by Russo, Rosalina & Co., LPA Visit us at http://www.rrlpa.com The importance of an estate plan was recently highlighted by a story out of New York when a 97 year-old man died without a will. The reason the man's story gained national attention: he was worth almost $40 million. The millionaire was a successful real estate developer who owned multiple pieces of property, valuable pieces of furniture and jewelry. He was a Holocaust survivor who married a fellow survivor ...

Will Truck Accident Rates Be Affected By Increased Weight Limits?

2013-05-15
Will Truck Accident Rates Be Affected By Increased Weight Limits? Article provided by Elk & Elk Co., Ltd. Visit us at http://www.elkandelktoledo.com There was opposition to a proposal to raise truck weight limits on the Ohio Turnpike, according to a story in the Toledo Blade. Proponents of increased weight limits argued that it would save fuel, spur economic development, and bring Ohio in line with other states with higher weight limits. Opponents say that longer and heavier trucks will increase road maintenance costs and result in more severe accidents. ...

Henri Richard Joins TNI Racing as Team Driver

2013-05-15
TNI Racing announces the joining of Henri Richard as a new team driver and coach. Richard will pilot one of TNI's Mazdaspeed 3 racecars in the 2013 Nitto Tire United States Touring Car Championship (USTCC) beginning mid-season. His extensive experience in professional racing and motorsports marketing will add depth to the TNI team. "TNI Racing is thrilled to add Henri's proven professional racing results and extensive team management experience to our organization," said Ron Valtierra, TNI team owner. "To prepare for a full 2014 season, we are planning ...

LAST 30 PRESS RELEASES:

Sensing sickness

Cost to build multifamily housing in California more than twice as high as in Texas

Program takes aim at drinking, unsafe sex, and sexual assault on college campuses

Inability to pay for healthcare reaches record high in U.S.

Science ‘storytelling’ urgently needed amid climate and biodiversity crisis

KAIST Develops Retinal Therapy to Restore Lost Vision​

Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response

Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid

Low LDL cholesterol levels linked to reduced risk of dementia

Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients

Almost one in ten people surveyed report having been harmed by the NHS in the last three years

Enhancing light control with complex frequency excitations

New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients

New insight into factors associated with a common disease among dogs and humans

Illuminating single atoms for sustainable propylene production

New study finds Rocky Mountain snow contamination

Study examines lactation in critically ill patients

UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award

Doubling down on metasurfaces

New Cedars-Sinai study shows how specialized diet can improve gut disorders

Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana

PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation

ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy

How VR technology is changing the game for Alzheimer’s disease

A borrowed bacterial gene allowed some marine diatoms to live on a seaweed diet

Balance between two competing nerve proteins deters symptoms of autism in mice

Use of antifungals in agriculture may increase resistance in an infectious yeast

Awareness grows of cancer risk from alcohol consumption, survey finds

The experts that can outsmart optical illusions

Pregnancy may reduce long COVID risk

[Press-News.org] Study IDs key protein for cell death