NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length.

Autor:	Karlsen TR; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Olsen MB; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Kong XY; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Yang K; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Quiles-Jiménez A; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Kroustallaki P; Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway., Holm S; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Lines GT; Simula Research Laboratory, Oslo, Norway., Aukrust P; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway., Skarpengland T; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway., Bjørås M; Department of Microbiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Dahl TB; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital HF, Rikshospitalet, Norway., Nilsen H; Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway., Gregersen I; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Halvorsen B; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Biochemistry and biophysics reports [Biochem Biophys Rep] 2022 Jan 18; Vol. 29, pp. 101211. Date of Electronic Publication: 2022 Jan 18 (Print Publication: 2022).
DOI:	10.1016/j.bbrep.2022.101211
Abstrakt:	Deficiency of NEIL3, a DNA repair enzyme, has significant impact on mouse physiology, including vascular biology and gut health, processes related to aging. Leukocyte telomere length (LTL) is suggested as a marker of biological aging, and shortened LTL is associated with increased risk of cardiovascular disease. NEIL3 has been shown to repair DNA damage in telomere regions in vitro . Herein, we explored the role of NEIL3 in telomere maintenance in vivo by studying bone marrow cells from atherosclerosis-prone NEIL3-deficient mice. We found shortened telomeres and decreased activity of the telomerase enzyme in bone marrow cells derived from Apoe -/- Neil3 -/- as compared to Apoe -/- mice. Furthermore, Apoe -/- Neil3 -/- mice had decreased leukocyte levels as compared to Apoe -/- mice, both in bone marrow and in peripheral blood. Finally, RNA sequencing of bone marrow cells from Apoe -/- Neil3 -/- and Apoe -/- mice revealed different expression levels of genes involved in cell cycle regulation, cellular senescence and telomere protection. This study points to NEIL3 as a telomere-protecting protein in murine bone marrow in vivo . (© 2022 The Authors.)
Databáze:	MEDLINE
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