Related Experiment Video

Updated: May 25, 2026

Minimal Erythema Dose (MED) Testing
06:24

Minimal Erythema Dose (MED) Testing

Published on: May 28, 2013

Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity

Yongxue Yao1, Kathleen A Harrison, Mohammed Al-Hassani

  • 1Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

The Journal of Biological Chemistry
|February 4, 2012
PubMed

Insights

Oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity are key drivers of photosensitivity in xeroderma pigmentosum type A (XPA) deficiency. Antioxidants and PAF receptor antagonists mitigate these effects, revealing a novel therapeutic target.

Area of Science:

  • Biochemistry
  • Dermatology
  • Genetics

Background:

  • Xeroderma pigmentosum type A (XPA) deficiency impairs DNA repair, leading to increased photosensitivity.
  • XPA-deficient cells exhibit reduced antioxidant defenses.
  • Non-enzymatic oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity are implicated in disease but lack defined roles.

Purpose of the Study:

  • To investigate the role of Ox-GPCs in the photosensitivity associated with XPA deficiency.
  • To determine if Ox-GPCs mediate UVB-induced skin inflammation in XPA-deficient models.

Main Methods:

  • Treatment of human XPA-deficient fibroblasts and Xpa-/- mice with ultraviolet B (UVB) radiation.
  • Measurement of reactive oxygen species (ROS) and PAF receptor (PAF-R) agonistic activity.
  • Inhibition studies using antioxidants and PAF-R antagonists.
  • Mass spectrometry for structural characterization of Ox-GPCs.

Main Results:

  • UVB irradiation increased ROS and PAF-R agonistic activity in XPA-deficient cells and mice.
  • Antioxidants and PAF-R antagonists inhibited UVB-induced PAF-R agonistic activity and skin inflammation.
  • Mass spectrometry identified increased sn-2 short-chain Ox-GPCs and PAF in UVB-irradiated XPA-deficient fibroblasts.
  • UVB-induced skin inflammation and TNF-α production in Xpa-/- mice were significantly reduced by antioxidants and PAF-R antagonists.

Conclusions:

  • Oxidized glycerophosphocholines (Ox-GPCs) play a critical role in the photosensitivity of xeroderma pigmentosum type A (XPA).
  • UVB-induced Ox-GPCs activate the PAF receptor, contributing to skin inflammation.
  • Targeting Ox-GPCs and the PAF receptor pathway offers a potential therapeutic strategy for XPA photosensitivity.

More Related Videos

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ10:05

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ

Published on: May 8, 2020

Related Concept Videos

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...
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...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Photoreceptors and Visual Pathways01:22

Photoreceptors and Visual Pathways

At the molecular level, visual signals trigger transformations in photopigment molecules, resulting in changes in the photoreceptor cell's membrane potential. The photon's energy level is denoted by its wavelength, with each specific wavelength of visible light associated with a distinct color. The spectral range of visible light, classified as electromagnetic radiation, spans from 380 to 720 nm. Electromagnetic radiation wavelengths exceeding 720 nm fall under the infrared category, whereas...