김규리 (동아대학교)

한빛사 논문

조회214

김규리Gyuri Kim

동아대학교

CV File 281 kb

J. Hazard. Mater., Nov 10 2023, 464 S0304-3894(23)02250-1 | https://doi.org/10.1016/j.jhazmat.2023.132966 Disruption of phosphofructokinase activity and aerobic glycolysis in human bronchial epithelial cells by atmospheric ultrafine particulate matter

Su Hwan Park ^a,1, Gyuri Kim ^a,1, Gi-Eun Yang ^a, Hye Jin Yun ^a, Tae Hwan Shin ^b, Sun Tae Kim^c, Kyuhong Lee ^d, Hyuk Soon Kim ^a,b, Seok-Ho Kim ^a, Sun-Hee Leem ^a,b, Wan-Seob Cho^a, Jong-Ho Lee^a,b

^aDepartment of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea

^bDepartment of Biomedical Sciences, Dong-A University, Busan 49315, Republic of Korea

^cDepartment of Plant Bioscience, Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea

^dInhalation Toxicology Center for Airborne Risk Factor, Korea Institute of Toxicology, 30 Baehak1-gil, Jeongeup, Jeollabuk-do, 56212, Republic of Korea

¹SHP and GK contributed equally to this work.

Corresponding authors : Sun-Hee Leem, Wan-Seob Cho, Jong-Ho Lee

Abstract

Exposure to ambient ultrafine particulate matter (UPM) causes respiratory disorders; however, the underlying molecular mechanisms remain unclear. In this study, we synthesized simulated UPM (sUPM) with controlled physicochemical properties using the spark-discharge method. Subsequently, we investigated the biological effects of sUPM using BEAS-2B human bronchial epithelial cells (HBECs) and a mouse intratracheal instillation model. High throughput RNA-sequencing and bioinformatics analyses revealed that dysregulation of the glycolytic metabolism is involved in the inhibited proliferation and survival of HBECs by sUPM treatment. Furthermore, signaling pathway and enzymatic analyses showed that the treatment of BEAS-2B cells with sUPM induces the inactivation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, also known as AKT), resulting in the downregulation of phosphofructokinase 2 (PFK2) S483 phosphorylation, PFK enzyme activity, and aerobic glycolysis in HBECs in an oxidative stress-independent manner. Additionally, intratracheal instillation of sUPM reduced the phosphorylation of ERK, AKT, and PFK2, decreased proliferation, and increased the apoptosis of bronchial epithelial cells in mice. The findings of this study imply that UPM induces pulmonary toxicity by disrupting aerobic glycolytic metabolism in lung epithelial cells, which can provide novel insights into the toxicity mechanisms of UPM and strategies to prevent their toxic effects.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-19)
연구진국내 연구진
분야 생명과학 > 분자생물학

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