The physiological unfolded protein response in the thyroid epithelial cells.
The perturbation of the endoplasmic reticulum (ER) homeostasis by the pharmacological agents or mutant secretory proteins invokes the adaptive cellular reaction, unfolded protein response (UPR). Here we show the activation of UPR under the physiological conditions of the hormone-stimulated expression of thyroglobulin (Tg), the major secretory product of thyroid cells. The early increase in the Tg synthesis within 1h after stimulation apparently triggers UPR as it is evidenced by the activation of ATF6- and PERK-dependent pathways of UPR and subsequent expression of the UPR target genes, ER molecular chaperones. However, little or no activation of the other UPR sensor, IRE1, was observed, as judged by the absence of the spliced mRNA of its downstream effector, transcription factor XBP1. We conclude that the physiological UPR in differentiating thyrocytes differs substantially from the drug-induced stress by its weaker manifestation and distinct pattern of the activation of UPR sensors.
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institute, 171 77, Stockholm, Sweden.
Ernest
E
Sargsyan
Mikhail
M
Baryshev
Souren
S
Mkrtchian
D051702:Activating Transcription Factor 6; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D007700:Kinetics; D008840:Microfilament Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D000071701:Regulatory Factor X Transcription Factors; D013961:Thyroid Gland / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1
D051702:Activating Transcription Factor 6; C497113:Atf6 protein, rat; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D018832:Molecular Chaperones; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat; C051615:transgelin