Oral Presentation 18th International Congress on Photobiology 2024

cNOS: A Key Regulator of Redox Homeostasis and DNA-damage Repair in Skin Cells Post-UV Exposure (#118)

Shiyong Wu 1 , Veronica Bahamondes Lorca 1 , Lingying Tong 1
  1. Ohio University, Athens, OHIO, United States

Ultraviolet (UV) radiation triggers a rapid increase in nitric oxide (NO·) production by constitutive nitric oxide synthases (cNOS), which disrupts cellular redox homeostasis. This surge in NO· has a complex relationship with DNA damage and repair in skin cells. Upon UV exposure, cNOS is activated and produces NO·, which readily reacts with superoxide (O2) to form peroxynitrite (ONOO-), a potent inducer of cyclobutane pyrimidine dimers (CPDs) - a hallmark of UV-induced DNA damage. Our study suggests cNOS also plays a critical role in DNA repair mechanisms post-UV. To unravel this paradox, we investigated the influence of cNOS on DNA damage and repair using cultured skin cells, skin explants, and SKH-1 mouse models. We observed that inhibiting cNOS activity indeed reduced markers of UV-induced DNA damage like γH2AX and CPD formation. However, this seemingly beneficial effect was countered by a concurrent impairment in DNA repair capacity after UV exposure in cNOS-deficient models as cNOS knockout leads to a slight increase of CPD inmediately after UV exposure which persists over the time. These findings suggest a dual role for cNOS: on one hand, it can contribute to DNA damage through NO· and ONOO- production, while on the other hand, it appears to be essential for efficient DNA repair mechanisms following UV irradiation.