Related Experiment Video

Updated: Apr 18, 2026

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
12:37

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model

Published on: September 7, 2013

18.9K

Endothelin-1 protects human melanocytes from UV-induced DNA damage by activating JNK and p38 signalling pathways

Anne M von Koschembahr1, Viki B Swope, Renny J Starner

  • 1Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Experimental Dermatology
|January 22, 2015
PubMed

Insights

Endothelin-1 signaling protects human melanocytes from UV damage by reducing DNA photoproducts and inhibiting apoptosis. This involves activating MAP kinases JNK and p38, crucial for genomic stability.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Cell Biology

Background:

  • Endothelin-1 (ET-1) is a paracrine factor influencing melanocyte behavior.
  • UV radiation induces DNA damage and apoptosis in melanocytes.
  • Understanding ET-1's role in UV response is crucial for skin protection.

Purpose of the Study:

  • To investigate the effects of ET-1 signaling on UV-induced DNA damage and melanocyte survival.
  • To elucidate the molecular pathways, including MAP kinases, involved in ET-1's protective effects.

Main Methods:

  • Cultured human melanocytes were treated with ET-1 and exposed to UV radiation.
  • Analysis of DNA photoproducts, apoptosis markers, and MAP kinase activation (JNK, p38, ATF-2 phosphorylation).
  • Investigated the role of endothelin B receptor and intracellular calcium signaling.

Main Results:

  • ET-1 reduced UV-induced DNA photoproducts and inhibited apoptosis without affecting proliferation or melanin content.
  • ET-1 activated JNK and p38 MAP kinases, enhancing their phosphorylation by UV.
  • These effects were dependent on endothelin B receptor signaling and calcium mobilization.

Conclusions:

  • ET-1 signaling, via endothelin B receptors, protects melanocytes from UV genotoxicity.
  • Activation of JNK and p38 MAP kinases by ET-1 is essential for reducing DNA damage and promoting cell survival.
  • ET-1 contributes to maintaining melanocyte genomic stability under UV stress.
Keywords:
Endothelin-1JNKhuman melanocytesp38ultraviolet radiation

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

9.7K
Y-27632 Enriches the Yield of Human Melanocytes from Adult Skin Tissues08:06

Y-27632 Enriches the Yield of Human Melanocytes from Adult Skin Tissues

Published on: July 8, 2020

6.2K

Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
6.0K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
42.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.5K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
46.7K
Pigmentation01:19

Pigmentation

The color of the skin is influenced by a number of pigments, including melanin, carotene, and hemoglobin. Recall that melanin is produced by cells called melanocytes, which are found scattered throughout the stratum basale of the epidermis. The melanin is transferred to the keratinocytes via melanosomes.
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
5.1K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.3K