한빛사논문
- 조회787
Hae-Ryung Park a, David Azzara a, Ethan D. Cohen b, Steven R. Boomhower c, Avantika R. Diwadkar d, Blanca E. Himes d, Michael A. O'Reilly b, Quan Lu c
aDepartment of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY
bDepartment of Pediatrics, School of Medicine and Dentistry, University of Rochester, Rochester, NY
cDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA
dDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA
Correspondence to: Hae-Ryung Park
Abstract
Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood. Here, we identified F2RL2, TRIM16L, and PANX2 as novel targets of Nuclear factor erythroid 2-related factor 2 (NRF2)—the master transcriptional factor for the oxidative stress response—that are commonly upregulated with both Pb and As in human neural progenitor cells (NPCs). Using a ChIP (Chromatin immunoprecipitation)-qPCR assay, we showed that NRF2 directly binds to the promoter region of F2RL2, TRIM16L, and PANX2 to regulate expression of these genes. We demonstrated that F2RL2, PANX2, and TRIM16L have differential effects on cell death, proliferation, and differentiation of NPCs in both the presence and absence of metal exposures, highlighting their roles in regulating NPC function. Furthermore, the analyses of the transcriptomic data on NPCs derived from autism spectrum disorder (ASD) patients revealed that dysregulation of F2RL2, TRIM16L, and PANX2 was associated with ASD genetic backgrounds and ASD risk genes. Our findings revealed that Pb and As induce a shared NRF2-dependent transcriptional response in NPCs and identified novel genes regulating NPC function. While further in vivo studies are warranted, this study provides a novel mechanism linking metal exposures to NPC function and identifies potential genes of interest in the context of neurodevelopment.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-06)
- 국외 연구진
- 생명과학 > 세포생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
