Featured Research

from universities, journals, and other organizations

New, surprising link between chloracne and molecule that protects cells against stress

Date:
February 6, 2014
Source:
ETH Zurich
Summary:
Researchers have discovered a new, surprising link between chloracne and a molecule that protects cells against stress: if Nrf2 gets out of control, disfiguring cysts form on the skin. Nrf2 is thus an interesting candidate for use in skincare creams and for cancer prevention.

ETH-Zurich researchers have discovered a new, surprising link between chloracne and a molecule that protects cells against stress: if Nrf2 gets out of control, disfiguring cysts form on the skin.

The images were seen all over the world and stuck in the minds of many: in the autumn of 2004, former President of the Ukraine, Viktor Yushchenko, was poisoned with a high dose of dioxin. Although he survived the attack, the chloracne caused by the poisoning, officially known as MADISH, left him severely disfigured: his face was peppered with numerous cysts, which left deep scars.

Now a team of researchers headed by ETH-Zurich professor Sabine Werner and a senior researcher of her team, Dr. Matthias Schäfer, has stumbled across a link between chloracne and a molecular switch, which causes a comparable skin phenotype in mice after longer and increased activation. The new discovery has just been published in EMBO Molecular Medicine.

Interesting candidate

The molecular switch is Nrf2, which the ETH-Zurich researchers have been studying in connection with different skin diseases for some time. Nrf2 is a so-called transcription factor. It activates certain genes that protect cells and help them to survive under stress conditions. The ETH-Zurich scientists had discovered that a moderate activation of Nrf2 protects the skin against UV damage (see ETH Life from 20 May 2010). The molecule activates several genes designed to protect skin cells from aggressive free radicals, which are formed through UV radiation, save them from dying off and prevent damage of the genetic material.

Nrf2 is thus an interesting candidate for use in skincare creams and for cancer prevention. Until now, however, the consequences of prolonged Nrf2 activation in the skin had not been characterized. After all, in a previous study Werner and Schäfer realised that the skin of mice became flaky and was thus potentially damaged upon increased activation of Nrf2.

Striking parallels between mice and humans

For their follow-up study, they used an animal model in which the skin cells of genetically modified mice permanently activated Nrf2. As a result, the animals developed skin changes that were strikingly similar to those in dioxin victims, albeit far less pronounced than in humans. In mice with Nrf2 activation, the sebaceous glands became enlarged and secreted an excessive amount of sebum. The hair follicles were also thickened and callused, which ultimately led to their widening, hair loss and eventually the development of cysts.

Consequently, in a second step the scientists tested tissue samples from MADISH patients and discovered that Nrf2 was evidently activated in their skin, causing a strong expression of the same target proteins as in the mouse model. Therefore, it is very likely that the processes that trigger such abnormal skin changes in mice also take place very similarly in humans.

Lady Luck has a hand

"We only spotted the link between chloracne and the mouse model in the course of our project -- purely by chance," says Werner. Originally, the aim had been to understand what takes place in the event of an increased activation of Nrf2 in the skin. Hence, the ETH-Zurich researchers are all the more delighted that they identified a major player in the development of chloracne.

The issue of which molecular mechanisms take place in an early phase of chloracne still remains unexplored. The researchers simply lack the samples from patients, who have suffered from dioxin poisoning, to address this question. Schäfer stresses how difficult it is to get hold of this kind of sample material. "The patients only go to the doctor once the condition is already quite advanced," he says. "In other words, the early stage goes undetected and is lost."

The two researchers believe, however, that therapeutic targeting of Nrf2 in the case of chloracne is problematic. The cells activate Nrf2 in order to accelerate the detoxification of the body. In the event of dioxin poisoning, slowing down or even stopping the body's response with an intervention against Nrf2 could be fatal. Besides, dioxin is a very long-lived toxin that is stored in the body's fatty tissue. It is no coincidence that precisely the sebaceous glands of the facial skin are changed so severely in the case of MADISH: lipids and thus dioxin are stored in them. Consequently, the researchers consider it more sensible to first examine Nrf2's target genes in more detail, so that the amount of activity of specific proteins that are responsible for the symptoms might potentially be influenced.


Story Source:

The above story is based on materials provided by ETH Zurich. The original article was written by Peter Rüegg. Note: Materials may be edited for content and length.


Journal Reference:

  1. Matthias Schäfer, Ann-Helen Willrodt, Svitlana Kurinna, Andrea S Link, Hany Farwanah, Alexandra Geusau, Florian Gruber, Olivier Sorg, Aaron J Huebner, Dennis R Roop, Konrad Sandhoff, Jean-Hilaire Saurat, Erwin Tschachler, Marlon R Schneider, Lutz Langbein, Wilhelm Bloch, Hans-Dietmar Beer and Sabine Werner. Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice. EMBO Molecular Medicine, February 2014 DOI: 10.1002/emmm.201303281

Cite This Page:

ETH Zurich. "New, surprising link between chloracne and molecule that protects cells against stress." ScienceDaily. ScienceDaily, 6 February 2014. <www.sciencedaily.com/releases/2014/02/140206111414.htm>.
ETH Zurich. (2014, February 6). New, surprising link between chloracne and molecule that protects cells against stress. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2014/02/140206111414.htm
ETH Zurich. "New, surprising link between chloracne and molecule that protects cells against stress." ScienceDaily. www.sciencedaily.com/releases/2014/02/140206111414.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) — Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) — Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) — At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) — The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:  

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile iPhone Android Web
      Follow Facebook Twitter Google+
      Subscribe RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins