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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...
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Related Experiment Video

Updated: May 1, 2026

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
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α-MSH Induces Intracellular ROS Generation in Melanoma Cells through NADPH Oxidase-1/4 Activation.

Kyuri Kim1, Jihyun Yoon1, Hye Yeon Kim1

  • 1College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea.

Biomolecules & Therapeutics
|April 30, 2026
PubMed
Summary

Alpha-melanocyte-stimulating hormone (α-MSH) triggers melanogenesis via reactive oxygen species (ROS). This study identifies cytosolic NADPH oxidases NOX1 and NOX4 as key mediators of α-MSH-induced ROS production in melanoma cells.

Keywords:
MelanogenesisNADPH oxidasesReactive oxygen speciesp38 MAP kinaseα-MSH

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Dermatology

Background:

  • Alpha-melanocyte-stimulating hormone (α-MSH) regulates melanogenesis and melanocyte activation.
  • Reactive oxygen species (ROS) act as signaling molecules in α-MSH-mediated pathways.
  • The precise mechanism of α-MSH-induced ROS generation in melanocytes requires further elucidation.

Purpose of the Study:

  • To investigate the sources and regulatory mechanisms of α-MSH-induced ROS in melanoma cells.
  • To identify the specific enzymes responsible for ROS production stimulated by α-MSH.
  • To assess the role of these ROS-producing enzymes in melanogenesis and MITF signaling.

Main Methods:

  • Utilized confocal microscopy to visualize ROS generation in B16F10 and MNT-1 melanoma cells.
  • Employed Western blot analysis to examine the expression of NADPH oxidases (NOX1, NOX4).
  • Applied pharmacological inhibitors to assess the impact of NOX1/4 on ROS levels, melanin content, and MITF phosphorylation.

Main Results:

  • α-MSH predominantly induced cytosolic ROS generation, not mitochondrial.
  • α-MSH upregulated the expression of NOX1 and NOX4 at early time points.
  • Inhibition of NOX1/4 decreased α-MSH-induced ROS, melanin content, and MITF phosphorylation.

Conclusions:

  • α-MSH stimulates melanogenesis and melanocyte signaling through ROS generation.
  • NOX1 and NOX4 are identified as crucial mediators of α-MSH-induced ROS in melanoma cells.
  • NOX1 and NOX4 represent potential therapeutic targets for anti-pigmentation strategies.