{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:21:28Z","timestamp":1787725288921,"version":"build-2784847793"},"reference-count":67,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32002193"],"award-info":[{"award-number":["32002193"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["CARS-42"],"award-info":[{"award-number":["CARS-42"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["CXGC-IAS-09"],"award-info":[{"award-number":["CXGC-IAS-09"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Agriculture Research System of MOF and MARA","award":["32002193"],"award-info":[{"award-number":["32002193"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-42"],"award-info":[{"award-number":["CARS-42"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CXGC-IAS-09"],"award-info":[{"award-number":["CXGC-IAS-09"]}]},{"name":"Chinese Academy of Agricultural Sciences","award":["32002193"],"award-info":[{"award-number":["32002193"]}]},{"name":"Chinese Academy of Agricultural Sciences","award":["CARS-42"],"award-info":[{"award-number":["CARS-42"]}]},{"name":"Chinese Academy of Agricultural Sciences","award":["CXGC-IAS-09"],"award-info":[{"award-number":["CXGC-IAS-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Riboflavin is an essential micronutrient and a precursor of flavin mononucleotide and flavin adenine dinucleotide for maintaining cell homeostasis. Riboflavin deficiency (RD) induces cell apoptosis. Endoplasmic reticulum (ER) stress is considered to induce apoptosis, and C\/EBP homologous protein (CHOP) is a key pathway involved in this process. However, whether RD-induced apoptosis is mediated by ER stress and the CHOP pathway remains unclear and needs further investigation. Therefore, the current study presents the effect of RD on ER stress and apoptosis in the human hepatoma cell line (HepG2). Firstly, cells were cultured in a RD medium (4.55 nM riboflavin) and a control (CON) medium (1005 nM riboflavin). We conducted an observation of cell microstructure characterization and determining apoptosis. Subsequently, 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, was used in HepG2 cells to investigate the role of ER stress in RD-induced apoptosis. Finally, CHOP\u00a0siRNA was transfected into HepG2 cells to validate whether RD triggered ER stress-mediated apoptosis by the CHOP pathway. The results show that RD inhibited cell proliferation and caused ER stress, as well as increased the expression of ER stress markers (CHOP, 78 kDa glucose-regulated protein, activating transcription factor 6) (p &lt; 0.05). Furthermore, RD increased the cell apoptosis rate, enhanced the expression of proapoptotic markers (B-cell lymphoma 2-associated X, Caspase 3), and decreased the expression of the antiapoptotic marker (B-cell lymphoma 2) (p &lt; 0.05). The 4-PBA treatment and CHOP knockdown markedly alleviated RD-induced cell apoptosis. These results demonstrate that RD induces cell apoptosis by triggering ER stress and the CHOP pathway.<\/jats:p>","DOI":"10.3390\/nu14163356","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T03:15:27Z","timestamp":1660706127000},"page":"3356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Riboflavin (Vitamin B2) Deficiency Induces Apoptosis Mediated by Endoplasmic Reticulum Stress and the CHOP Pathway in HepG2 Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Bo","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ting","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Bao","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Kui","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shui-Sheng","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0009-8981(69)90376-3","article-title":"Glutathione reductase activity in red blood cells and riboflavin nutritional status in humans","volume":"26","author":"Bamji","year":"1969","journal-title":"Clin. 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