The role of the IRE1 pathway in excessive iodide- and/or fluoride-induced apoptosis in Nthy-ori 3-1 cells in vitro.
Excessive iodide and fluoride coexist in the groundwater in many regions, causing a potential risk to the human thyroid. To investigate the mechanism of iodide- and fluoride-induced thyroid cytotoxicity, human thyroid follicular epithelial cells (Nthy-ori 3-1) were treated with different concentrations of potassium iodide (KI), with or without sodium fluoride (NaF). Cell morphology, viability, lactate dehydrogenase (LDH) leakage, apoptosis, and expression of inositol-requiring enzyme 1 (IRE1) pathway-related molecules were assessed. Results showed 50 mM of KI, 1 mM of NaF, and 50 mM of KI +1 mM of NaF changed cellular morphology, decreased viability, and increased LDH leakage and apoptosis. Elevated expression of binding protein (BiP), IRE1, and C/EBP homologous protein (CHOP) mRNA and protein, as well as spliced X-box-binding protein-1 (sXBP-1) mRNA, were observed in the 1 mM NaF and 50 mM KI +1 mM NaF groups. Collectively, excessive iodide and/or fluoride is cytotoxic to the human thyroid. Although these data do not manifest iodide could induce the IRE1 pathway, the cytotoxicity followed by exposure to fluoride alone or in combination with iodide may be related to IRE1 pathway-induced apoptosis. Furthermore, exposure to the combination of excessive iodide and fluoride may cause interactive effects on thyroid cytotoxicity.
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China. Electronic address: liuhongliang@cdctj.gov.cn.
Hongliang
H
Liu
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China.
Qiang
Q
Zeng
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China.
Yushan
Y
Cui
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China.
Liang
L
Zhao
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China.
Lei
L
Zhang
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China.
Gang
G
Fu
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China.
Changchun
C
Hou
Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, People's Republic of China.
Shun
S
Zhang
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China.
Linyu
L
Yu
Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, People's Republic of China.
Chunyang
C
Jiang
Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, People's Republic of China.
Zhenglun
Z
Wang
Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, People's Republic of China.
Xuemin
X
Chen
Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, People's Republic of China. Electronic address: wangaiguo@mails.tjmu.edu.cn.
Aiguo
A
Wang
D000199:Actins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004722:Endoribonucleases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005459:Fluorides / Q000633:toxicity*; D006801:Humans; D007454:Iodides / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D000199:Actins; C497249:DDIT3 protein, human; D017931:DNA Primers; D004268:DNA-Binding Proteins; D007454:Iodides; D008565:Membrane Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D007770:L-Lactate Dehydrogenase; C403982:ERN2 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D005459:Fluorides
Apoptosis; Fluoride; IRE1; Iodide; Thyroid