Tag: sunburn

Categories : Cancer DermatologyTags :

Controlling Inflammation from Sunburn May Prevent Skin Cancer

On By ModernMedia
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In a new study published in Nature Communications, researchers at the University of Chicago have discovered how prolonged exposure to ultraviolet (UV) radiation can trigger inflammation in skin cells through degradation of a key protein called YTHDF2. This protein acts as a gatekeeper in preventing normal skin cells from becoming cancerous. The finding reveals that YTHDF2 plays a crucial role in regulating RNA metabolism to keep cells in a healthy state and opens the door to developing potential new approaches to skin cancer prevention and treatment.

Uncontrolled inflammation triggers skin cancer

Each year, nearly 5.4 million people in the United States are diagnosed with skin cancer, with more than 90% of cases attributed to excessive UV exposure. UV rays can damage DNA and cause oxidative stress and inflammation in skin cells — leading to redness, pain and blistering, commonly known as sunburn.

“We’re interested in understanding how inflammation caused by UV exposure contributes to the development of skin cancer,” said Yu-Ying He, PhD, Professor of Medicine in the Section of Dermatology at the University of Chicago.

RNA or ribonucleic acid is an essential molecule that helps convert genetic information into proteins. A special class known as non-coding RNAs regulates gene expression without producing proteins. These molecules typically function in either the nucleus, where a cell’s DNA is stored or the cytoplasm, where most cellular activity occurs.

Low levels of YTHDF2 turn normal skin cells cancerous

He’s laboratory studies how environmental stressors, such as UV radiation or arsenic in drinking water, affect molecular pathways and damage cellular systems, leading to cancer. Through screening various enzymes, the researchers found that UV exposure causes a marked decrease in levels of YTHDF2, a “reader” protein that specifically binds to RNA sequences marked with a chemical tag known as N6-methyladenosine (m6A).

“When we removed YTHDF2 from skin cells, we saw that UV-triggered inflammation was much worse,” He said. “This suggests that the YTHDF2 protein plays a key role in suppressing inflammatory responses.”

Although inflammation is essential for fighting off infections, it also plays a major role in causing life-threatening diseases, including cancer. However, the molecular mechanisms that regulate this response, especially after UV damage, are not well understood.

YTHDF2 in regulation of non-coding RNA interactions

Using multi-omics analysis and additional cellular assays, the research team found that YTHDF2 binds to a specific non-coding RNA known as U6, which is modified by m6A and classified as a small nuclear RNA (snRNA). Under UV stress, cancer cells showed increased levels of U6 snRNA, and these modified RNAs were found to interact with toll-like receptor 3 (TLR3), an immune sensor known to activate inflammatory pathways linked to cancer.

Surprisingly, these interactions occurred within endosomes, where cellular compartments are typically involved in recycling materials, not where U6 snRNA is usually located.

“We spent a lot of time figuring out how these non-coding RNAs get to the endosome, since that’s not where they usually reside,” He explained. “For the first time, we showed that a protein called SDT2 transports U6 into the endosome, and YTHDF2 travels with it.”

Once both YTHDF2 and m6A-modified U6 RNA arrive at the endosome, YTHDF2 blocks the RNA from activating TLR3. However, when YTHDF2 is absent – such as after UV damage, the RNA freely binds to TLR3, triggering harmful inflammation.

“Our study uncovers a new layer of biological regulation, a surveillance system through YTHDF2 that helps protect the body from excessive inflammation and inflammatory damage,” He said.

The findings could open the door to new strategies for preventing or treating UV-induced skin cancer by targeting the RNA-protein interactions that regulate inflammation.

Source: University of Chicago Medicine

The study, “YTHDF2 regulates self non-coding RNA metabolism to control inflammation and tumorigenesis,” was supported by grants from the National Institutes of Health, the University of Chicago Medicine Comprehensive Cancer Center, the ChicAgo Center for Health and EnvironmenT (CACHET), and the University of Chicago Friends of Dermatology Endowment Fund.

Categories : DermatologyTags :

Sunburn Results from Damage to RNA, not DNA

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The warnings against sunburn are well known: avoid direct sunlight between 12 noon and 3pm, seek out shade and put on sunscreen and a hat. It is also taught that sunburn results from damage to DNA. But that is not the full truth, according the researchers behind a new study conducted at the University of Copenhagen and Nanyang Technological University, Singapore (NTU Singapore).

“Sunburn damages the DNA, leading to cell death and inflammation. So the textbooks say. But in this study we were surprised to learn that this is a result of damage to the RNA, not the DNA that causes the acute effects of sunburn,” says Assistant Professor Anna Constance Vind, who is one of the researchers responsible for the new study.

The study has been published in Molecular Cell.

RNA is a more transient molecule than DNA. A type of RNA, known as messenger RNA (mRNA), functions as the intermediate ‘messenger’ that carries information from DNA to make proteins – the basic building blocks of cellular components.

“DNA damage is serious as the mutations will get passed down to progenies of the cells, RNA damage happens all the time and does not cause permanent mutations. Therefore, we used to believe that the RNA is less important, as long as the DNA is intact. But in fact, damages to the RNA are the first to trigger a response to UV radiation,” Anna Constance Vind explains.

The new study was conducted on mice as well as human skin cells, and the objective was to describe the impact of UV radiation on the skin and what causes these damages. The researchers found the same skin response to UV radiation exists in both mice and human cells.

A built-in surveillance system for RNA damage

mRNA damage triggers a response in ribosomes (protein complexes that “read” the mRNA to synthesise protein), orchestrated by a protein known as ZAK-alpha – the so-called ribotoxic stress response – the new study shows. The response can be described as a surveillance system within the cells, which registers the RNA damage, leading to inflammatory signalling and recruitment of immune cells, which then leads to inflammation of the skin.

“We found that the first thing the cells respond to after being exposed to UV radiation is damage to the RNA, and that this is what triggers cell death and inflammation of the skin. In mice exposed to UV radiation we found responses such as inflammation and cell death, but when we removed the ZAK gene, these responses disappeared, which means that ZAK plays a key role in the skin’s response to UV-induced damage,” says Professor Simon Bekker-Jensen from the Department of Cellular and Molecular Medicine, who is one of the other researchers responsible for the study. He adds:

“So you could say that everything depends on this one response, which monitors all protein translations occurring. The cells respond to the RNA damage, realising that something is wrong, and this is what leads to cell death.”

Faster and more effective response

The result of the study changes our understanding of sunburn and the skin’s defence mechanisms: that RNA damage triggers a faster and more effective response, protecting the skin from further damage.

“The fact that the DNA does not control the skin’s initial response to UV radiation, but that something else does and that it does so more effectively and more quickly, is quite the paradigm shift,” says Anna Constance Vind.

We need to understand the function of RNA damage, as it may in the long term change our entire approach to prevention and treatment of sunburn.

“Many inflammatory skin diseases are worsened by sun exposure. Thus, understanding how our skin responds at the cellular level to UV damage opens the door to innovative treatments for certain chronic skin conditions,” says co-author Dr Franklin Zhong, Nanyang Assistant Professor at NTU’s Lee Kong Chian School of Medicine.

“This new knowledge turns things upside down. I think most people associate sunburn with DNA damage; it is established knowledge. But now we need to rewrite the textbooks, and it will affect future research on the effects of UV radiation on the skin,” Simon Bekker-Jensen concludes.

Source: University of Copenhagen

Categories : Diet and NutritionTags :

Eating Grapes Protects against Sunburn

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Compounds found in the humble grape may offer a protective effect against the sun’s damaging UV radiation, a new study has found.

Researchers from University of Alabama at Birmingham’s (UAB) Department of Dermatology found that healthy adult participants who ate freeze-dried powdered grapes for 14 days achieved a 74.8% increase in natural skin protection. 

The number of sunburns experienced over a lifetime increases the risk of skin cancer. Sunburns also cause skin damage, which has a cosmetic effect. Sunburns are marked by DNA damage triggering cell apoptosis, as well as the release of inflammatory markers such as prostaglandins, reactive oxygen species, and bradykinin in response to dimers formed by UV radiation. Prostaglandin E2 and histamine levels also rise after a sunburn.
Research in mouse models has shown that polyphenols, found in grapes as well as other fruits and vegetables, can reduce UV radiation damage, as well as reducing the production of inflammatory compounds. As such, this is the first research that shows the consumption of table grapes has a photoprotective effect against the sunburn response in adult humans. The subjects were also given a polyphenol compound, proanthocyanidin, as a topical extract to apply on their skin.

“Study results indicate that oral consumption of grapes has systemic beneficial effects in healthy adults,” said lead author Allen Oak, MD, a dermatologist in the UAB School of Medicine. “These benefits include inhibition of inflammation and repair of DNA damage.”

The preliminary findings also indicated that grapes may help reduce the risk of skin cancer as well, although this requires further research. 
“Grape consumption may act as an ‘edible sunscreen,'” Oak said. “This does not mean that grapes should be used in lieu of sunscreen, but they may offer additional protection which we are eager to continue learning more about. This research is exciting because our current findings provide building blocks for additional studies that may eventuate in an oral photoprotective product from a natural source.”

Source: Medical Xpress

Journal information: Allen S.W. Oak et al. Dietary table grape protects against UV photodamage in humans: 1. clinical evaluation, Journal of the American Academy of Dermatology (2021). DOI: 10.1016/j.jaad.2021.01.035