Tag: skin

Categories : DermatologyTags : Leave a comment

Researchers Stumble on Haemoglobin in the Epidermis

On By ModernMedia
Image by macrovector on Freepik

Researchers have shown for the first time that haemoglobin, a protein found in red blood cells where it binds oxygen, is also present in the epidermis. The study, which appears in the Journal of Investigative Dermatology, published by Elsevier, provides important insights into the properties of the skin’s protective external layer.

This research was driven by a curiosity about the protective role of the epidermis and what unexpected molecules are expressed in it. Researchers discovered the haemoglobin α protein in keratinocytes of the epidermis and in hair follicles. This unexpected evidence adds a new facet to the understanding of the workings of the skin’s defence mechanisms.

Lead investigator of the study Masayuki Amagai, MD, PhD, Department of Dermatology, Keio University School of Medicine, Tokyo, and Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, explains: “The epidermis consists of keratinised stratified squamous epithelium, which is primarily composed of keratinocytes. Previous studies have identified the expression of various genes with protective functions in keratinocytes during their differentiation and formation of the outer skin barrier. However, other barrier-related genes escaped prior detection because of difficulties obtaining adequate amounts of isolated terminally differentiated keratinocytes for transcriptome analysis.”

Haemoglobin binds gases such as oxygen, carbon dioxide, and nitric oxide, and it is an iron carrier via the heme complex. These properties make epidermal haemoglobin a prime candidate for antioxidant activity and potentially other roles in barrier function.

Professor Amagai continues: “We conducted a comparative transcriptome analysis of the whole and upper epidermis, both of which were enzymatically separated as cell sheets from human and mouse skin. We discovered that the genes responsible for producing haemoglobin were highly active in the upper part of the epidermis. To confirm our findings, we used immunostaining to visualise the presence of haemoglobin α protein in keratinocytes of the upper epidermis.”

Professor Amagai concludes: “Our study showed that epidermal haemoglobin was upregulated by oxidative stress and inhibited the production of reactive oxygen species in human keratinocyte cell cultures. Our findings suggest that haemoglobin α protects keratinocytes from oxidative stress derived from external or internal sources such as UV irradiation and impaired mitochondrial function, respectively. Therefore, the expression of haemoglobin by keratinocytes represents an endogenous defence mechanism against skin aging and skin cancer.”

Source: EurekAlert!

Categories : Cancer GeneticsTags : Leave a comment

New Study Finds Genetic Switch Role in Melanoma

On By ModernMedia
The ability of cancer cells to move and spread depends on actin-rich core structures such as the podosomes (yellow) shown here in melanoma cells. Cell nuclei (blue), actin (red), and an actin regulator (green) are also shown. Source: National Cancer Institute
Metastatic melanoma cells

A study published in the journal Cell Reports reveals that a genetic switch that could potentially be targeted to develop new treatments for melanoma by keeping the switch turned off.

Melanoma causes the majority of skin cancer-related deaths, despite only making up roughly 1 percent of skin cancers. The incidence of malignant melanoma is rapidly increasing around the world, and this increase is occurring at a faster rate than that of any other cancer except lung cancer in women. Treatments exist for this serious disease, but the effectiveness of these drugs can vary depending on the individual.

“We’ve been able to correlate the activity of this genetic switch to melanin production and cancer,” said Salk study corresponding author Marc Montminy, a professor in the Clayton Foundation Laboratories for Peptide Biology.

Melanoma develops when melanocytes, the pigment-producing skins in the cell, mutate and begin to multiply out of control. These mutations can cause proteins such as CRTC3 to prompt the cell to produce an abnormal amount of pigment, or to migrate and be more invasive.

While it was known that the CRTC family of proteins (CRTC1, CRTC2, and CRTC3) is involved in pigmentation and melanoma, obtaining precise details about the individual proteins has proven difficult. “This is a really interesting situation where different behaviours of these proteins, or genetic switches, can actually give us specificity when we start thinking about therapies down the road,” said first author Jelena Ostojic, a former Salk staff scientist and now a principal scientist at DermTech.

When the researchers deleted the CRTC3 gene in mice caused a color change in the animal’s coat color, demonstrating that the protein is needed for melanin production. They also found that when melanoma cells lacked the protein, they migrated and invaded less, meaning they were less aggressive, suggesting that inhibiting the protein could help treat the disease.

The team also described the connection between two cellular signalling systems that work on the CRTC3 protein in melanocytes. These two systems tell the cell to either proliferate or make the pigment melanin. Montminy likens this process to a relay race: essentially, a baton (chemical message) is passed from one protein to another until it reaches the CRTC3 switch, either turning it on or off.

“The fact that CRTC3 was an integration site for two signaling pathways—the relay race—was most surprising,” says Montminy, who holds the J.W. Kieckhefer Foundation Chair. “CRTC3 makes a point of contact between them that increases specificity of the signal.”

Next, the team plans to further investigate the mechanism of how CTRC3 impacts the balance of melanocyte differentiation to develop a better understanding of its role in cancer.

Source: Salk Institute