title: The induction of thioredoxin-1 by epinephrine withdraws stress via interaction with β-arrestin-1.
abstract: Stress regulates a panel of important physiological functions and disease states. Epinephrine is produced under stresses threaten to homeostasis. Thioredoxin-1(Trx-1) is a redox regulating protein which is induced to resist stresses and related with various diseases. Thus, it is important to examine whether Trx-1 is induced by epinephrine and to understand the underlying molecular mechanisms that Trx-1 modulates epinephrine stress. Here, we show that the expression of Trx-1 was induced by epinephrine via β-adrenergic receptor/Cyclic AMP/protein kinase A (PKA) signaling pathway in PC12 cells. The down-regulation of Trx-1 by siRNA aggravated accumulation of γ-H2AX and further decreased expression of p53 by epinephrine. Accordingly, Trx-1 overexpression alleviated accumulation of γ-H2AX and restored the expressions of p53 and C/EBP homologous protein (CHOP) in the cortex, hippocampus and thymus of mice. Moreover, Trx-1 overexpression reduced the malondialdehyde concentration by epinephrine. We further explored the mechanism on p53 and γ-H2AX regulated by Trx-1. We found that overexpression of Trx-1 suppressed β-arrestin-1 expression through interaction with β-arrestin-1. Consequently, the downregulation of β-arrestin-1 suppressed the cell viability and the expressions of γ-H2AX and cyclin D1, and increased p53 expression. Taken together, our data suggest that Trx-1/β-arrestin-1 interaction may represent a novel endogenous mechanism on protecting against stress.
authors.affiliation: a College of Life Science and Technology ; Kunming University of Science and Technology ; Kunming , China.
authors.forename: Jin-Jing
authors.initials: JJ
authors.lastname: Jia
authors.forename: Xian-Si
authors.initials: XS
authors.lastname: Zeng
authors.forename: Xiao-Shuang
authors.initials: XS
authors.lastname: Zhou
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016716:PC12 Cells; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
chemical_list: C000605253:ARRB1 protein, human; C000605255:Arrb1 protein, mouse; C000605256:Arrb1 protein, rat; D019390:Arrestins; C497251:Ddit3 protein, rat; D034741:RNA, Small Interfering; D011943:Receptors, Adrenergic, beta; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D019938:Cyclin D1; D051742:Transcription Factor CHOP; D008315:Malondialdehyde; D013879:Thioredoxins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004837:Epinephrine
keywords: ASK1, Apoptosis signal-regulating kinase 1; Abbreviations:; CHOP; CHOP, C/EBP homologous protein; DNA damage; GPCR, G protein-coupled receptors; MAPK, Mitogen-activated protein kinase; MDA, Malondialdehyde; MDM2, Murine double minute 2; PKA, Protein Kinase A; TBP-2, Thioredoxin binding protein-2; Thioredoxin-1; Trx-1, Thioredoxin-1; Txnip, thioredoxin interacting protein; chronic epinephrine stress; p53; β-arrestin-1; γ-H2AX, Phosphorylation of histone H2AX