Neurons and astrocytes exhibit lower activities of global genome nucleotide excision repair than do fibroblasts

• Published in: DNA repair 2007-05, Vol.6 (5), p.649-657
• Main Authors: Yamamoto, Aya, Nakamura, Yu, Kobayashi, Nobuhiko, Iwamoto, Takaaki, Yoshioka, Akira, Kuniyasu, Hiroki, Kishimoto, Toshifumi, Mori, Toshio
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Astrocytes - pathology; Astrocytes - radiation effects; Bacteriology; Biological and medical sciences; Brain - embryology; Brain - pathology; Brain - radiation effects; Bromodeoxyuridine; Cells, Cultured; Dermatology; DNA - genetics; DNA - radiation effects; DNA Damage; DNA Repair; Embryo, Mammalian - pathology; Embryo, Mammalian - radiation effects; Fibroblasts - pathology; Fibroblasts - radiation effects; Fundamental and applied biological sciences. Psychology; Genome; Growth, nutrition, cell differenciation; Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue; Medical sciences; Microbiology; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Neurodegeneration; Neurons; Neurons - pathology; Neurons - radiation effects; Nucleotide excision repair; Proliferating Cell Nuclear Antigen; Radiation Tolerance; Rats; Ultraviolet Rays; Xeroderma pigmentosum
• ISSN: 1568-7864; 1568-7856
• DOI: 10.1016/j.dnarep.2006.12.006

Nucleotide excision repair (NER) is a DNA repair pathway, which eliminates various types of helix-distorting DNA damage including some forms of oxidative damage and UV-induced photoproducts. To understand why patients with NER-defective disorders develop progressive neurological abnormalities, we investigated NER capabilities in neural cells. Primary cultured neurons and astrocytes derived from rat embryonic brains were prepared in mixed-cell cultures, and fibroblasts from the same embryos were cultured for comparison. Neurons in culture were unable to proliferate, while cultured astrocytes maintained that capacity. Determination of (6-4) photoproducts in situ using antibodies against those DNA lesions was used to measure NER capabilities in individual neural cells, which were identified by staining with specific cell markers. The results demonstrate that both neurons and astrocytes have significantly lower NER capabilities than fibroblasts. That result was consistent with the finding that levels of an NER-related protein (proliferating cell nuclear antigen, PCNA) recruited at the localized UV-damage sites were lower in neurons and in astrocytes than in fibroblasts. Interestingly, the degrees of NER deterioration in those neural cells were almost equivalent to those found in NER-defective human fibroblasts (TTD2VI) that show an increased sensitivity to UV. Thus, the present study suggests that an attenuated NER capacity is not specific to post-mitotic neurons, but may be common to neural cells constituting the central nervous system regardless of their residual proliferative capacity. Although the reduced but substantial NER capability of neural cells is indispensable to preventing progressive neurological abnormalities, that low NER capability might have implications for brain ageing.