Melanogenesis is a major part of the environmental responses and tissue development of the integumentary system. The balance between reduction and oxidation (redox) governs pigmentary responses, for which coordination among epidermal resident cells is indispensable. Here, we review the current understanding of melanocyte biology with a particular focus on the "master regulator" of oxidative stress responses (i.e., the Kelch-like erythroid cell-derived protein with cap'n'collar homology-associated protein 1-nuclear factor erythroid-2-related factor 2 system) and the autoimmune pigment disorder vitiligo. Our investigation revealed that the former is essential in pigmentogenesis, whereas the latter results from unbalanced redox homeostasis and/or defective intercellular communication in the interfollicular epidermis (IFE). Finally, we propose a model in which keratinocytes provide a "niche" for differentiated melanocytes and may "imprint" IFE pigmentation.
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http://dx.doi.org/10.3390/biom13010020 | DOI Listing |
Cell Death Dis
January 2025
Faculty of Medicine, Institute of Biochemistry I, Goethe University Frankfurt, Frankfurt, Germany.
Arachidonate 15-lipoxygenase type B (ALOX15B) peroxidises polyunsaturated fatty acids to their corresponding fatty acid hydroperoxides, which are subsequently reduced into hydroxy-fatty acids. A dysregulated abundance of these biological lipid mediators has been reported in the skin and blood of psoriatic compared to healthy individuals. RNAscope and immunohistochemistry revealed increased ALOX15B expression in lesional psoriasis samples.
View Article and Find Full Text PDFNuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor regulating cellular redox homeostasis, exhibits a complex role in cancer biology. Genetic mutations in the Kelch-like ECH-associated protein 1 (KEAP1)/NRF2 system, which lead to NRF2 hyperactivation, are found in 20% to 30% of lung cancer cases. This review explores the intricate interplay between NRF2 and key oncogenic pathways in lung cancer, focusing on the interaction of KEAP1/NRF2 system with Kirsten rat sarcoma virus (KRAS), tumor protein P53 (TP53), epidermal growth factor receptor (EGFR), and phosphatidylinositol 3-kinases (PI3K)/AKT signaling.
View Article and Find Full Text PDFSci Rep
January 2025
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Antibody-drug conjugates (ADCs) are an emerging strategy in cancer therapy, enhancing precision and efficacy by linking targeted antibodies to potent cytotoxic agents. This study introduces a novel ADC that combines ribonuclease A (RNase A) with cetuximab (Cet), an anti-EGFR monoclonal antibody, through a polyethylene glycol (PEG) linker (RN-PEG-Cet), aimed to induce apoptosis in KRAS mutant colorectal cancer (CRC) via a ROS-mediated pathway. RN-PEG-Cet was successfully synthesized and characterized for its physicochemical properties, retaining full enzymatic activity in RNA degradation and high binding affinity to EGFR.
View Article and Find Full Text PDFDis Model Mech
January 2025
Institute of Molecular Health Sciences, Department of Biology, ETH Zürich, 8093 Zürich, Switzerland.
Arch Dermatol Res
December 2024
Department of Dermatology, Jinshan Hospital of Fudan University, Shanghai, 201508, China.
This study explores the protective role of Atractylodin (ATN) on ultraviolet-B (UVB) radiation-exposed oxidative damage and photoaging responses in human epidermal keratinocytes (HaCaT). In vitro, experiments involved subjecting HaCaT cells to UVB radiation (50 mJ/cm) for a 24 h incubation period, leading to cell death, increased reactive oxygen species (ROS), and DNA damaged lesion (8-Oxo Gunosine). ATN treatment effectively mitigated cell toxicity, ROS generation, and 8-Oxo Gunosine in UVB-exposed HaCaT cells.
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