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Low-dose UV-radiation sensitizes keratinocytes to TRAIL-induced apoptosis

Jian-Zhong Qin1, Patricia Bacon, Jeffrey Panella

  • 1Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153, USA.

Journal of Cellular Physiology
|May 12, 2004
PubMed

Insights

Low-dose ultraviolet light (UV-light) increases keratinocyte (KC) susceptibility to TRAIL-induced apoptosis by reducing decoy receptors. This UV-light effect on apoptosis is mediated by mitochondrial pathways and decoy receptor levels.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Cell Biology

Background:

  • Skin is the primary target of UV-light exposure.
  • UV-light influences TRAIL death receptors, but the role of decoy receptors is unknown.
  • Apoptosis is crucial for eliminating UV-damaged cells and preventing skin cancer.

Purpose of the Study:

  • To investigate the impact of low-dose UV-light on keratinocyte (KC) apoptosis induced by TRAIL.
  • To determine the role of decoy receptors in UV-light-enhanced TRAIL-induced apoptosis.
  • To elucidate the molecular mechanisms underlying UV-light's effect on KC apoptotic sensitivity.

Main Methods:

  • Exposure of KCs to low-dose UV-light and TRAIL.
  • Analysis of decoy and death receptor levels.
  • Over-expression of decoy receptors (TRAIL-R4, TRAIL-R3) and manipulation of signaling molecules (PDTC, Bcl-x, FADD, caspase 9).
  • Assessment of mitochondrial pathways (cytochrome c, Smac release) and caspase activation.

Main Results:

  • Low-dose UV-light enhances KC susceptibility to TRAIL-induced apoptosis.
  • UV-light selectively reduces decoy receptors (TRAIL-R4, TRAIL-R3) without affecting death receptors.
  • Over-expression of TRAIL-R4, but not TRAIL-R3, or PDTC treatment, mitigated UV-light-enhanced apoptosis.
  • UV-light and TRAIL synergistically promoted mitochondrial release of cytochrome c and Smac.
  • Caspase inhibitors and dominant-negative constructs of FADD and caspase 9 reduced the apoptotic response.

Conclusions:

  • Decoy receptor levels significantly influence KC susceptibility to TRAIL-induced apoptosis under low-dose UV-light exposure.
  • UV-light enhances apoptosis through modulation of decoy receptors and mitochondrial permeabilization pathways.
  • Understanding these mechanisms is vital for comprehending cutaneous photocarcinogenesis.

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