Natural compound in broccoli could treat devastating genetic skin disorder

Dec 02, 2007

The compound sulforaphane whose natural precursors are found at high levels in broccoli and other cruciferous vegetables has been hailed for its chemopreventive powers against cancer. Now sulforaphane has demonstrated new skills in treating a genetic skin blistering disorder called epidermolysis bullosa simplex (EBS), Pierre Coulombe and colleagues at the Johns Hopkins University School of Medicine in Baltimore report at the American Society for Cell Biology 47th Annual Meeting.

EBS is a rare but devastating inherited condition in which fluid-filled lesions called bullae appear at sites of frictional trauma to the skin. Unfortunately, treatment options for EBS are limited and palliative in nature. Much work remains to be done before sulforaphane can be tested clinically with EBS patients, but Coulombe notes that extracts from broccoli sprouts rich in sulforaphane have already been shown to be safe for use in human skin.

In EBS patients, the bottom layer of the epidermis, which is made of cells called keratinocytes, is unusually fragile and ruptures readily. Molecularly, most cases of EBS result from mutations in genes that produce the proteins keratin 5 (K5) and keratin 14 (K14). These proteins co-polymerize to form the intermediate filament cytoskeleton in basal keratinocytes. Since the discovery in 1991 that EBS is a keratin-based disease, more than 40 additional disorders affecting a broad range of tissues have been traced to defects in genes that encode intermediate filament proteins.

Coulombe and colleagues turned to sulforaphane in their search for a chemical activator that would induce the production of missing keratins in basal epidermis. There are 54 “conserved” keratin proteins in mammals -- meaning that evolution favored their survival. Many of these keratins are closely related in their genetic sequences and their properties and by their distribution within epithelial tissues. Coulombe reasoned that such a situation breeds “functional redundancy,” meaning that the genetic loss of one keratin could be partially rescued by the overlapping functions of a keratin cousin.

Could this partial redundancy serve as the basis for therapy in EBS and related conditions? Coulombe was guided by prior evidence that partial redundancy was at work. In EBS patients, skin blisters heal without scarring, correlating with an induction in the expression of the protein K6, to which K5 is related, and of K17 and K16, to which K14 is related. In transgenic mouse models, these keratins are indeed partially redundant in their ability to provide structural support in skin keratinocytes.

Sulforaphane was originally identified by Johns Hopkins colleague, Paul Talalay, as the chemical entity in cruciferous vegetables responsible for its anti-cancer properties. As originally reported in the August 2007 issue of PNAS, the researchers found that exposing keratinocytes to sulforaphane caused the selective induction of keratins 16 and 17. Moving to an EBS mouse model with a K14 deficiency, they found that treatment with sulforaphane significantly reduced epidermal blistering while it was ineffective for a K5 deficient mouse.

Source: American Society for Cell Biology

Explore further: Culprit identified in decline of endangered Missouri River pallid sturgeon

add to favorites email to friend print save as pdf

Related Stories

Snapshot of cosmic burst of radio waves

1 hour ago

A strange phenomenon has been observed by astronomers right as it was happening - a 'fast radio burst'. The eruption is described as an extremely short, sharp flash of radio waves from an unknown source in ...

Journal team adds reviewer pay to open-access model

11 hours ago

A new open-access journal called Collabra plans to pay reviewers, and that's a twist in the world of scientific publishing. The reviewers get to exercise some options. They can keep the cash (generally a ...

Recommended for you

Kalbarri abalone gets helping hand

Jan 23, 2015

Department of Fisheries staff and Kalbarri fishermen have released 24,000 Roe's abalone (Haliotis roei) onto reef platforms along the cliffs north of Kalbarri, to restock a population decimated by the marine ...

Bad reputation of crows demystified

Jan 23, 2015

In literature, crows and ravens arebad omens and are associated with witches. Most people believe they steal, eat other birds' eggs and reduce the populations of other birds. But a new study, which has brought ...

How gerbils orient in the light of the setting sun

Jan 23, 2015

A light brown remains light brown: For gerbils, the fur color of their conspecifics appears identical under different lighting conditions. The ability of color constancy in rodents has been demonstrated for ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.