• Something wrong with this record ?

PKA/CREB and NF-κB pathway regulates AKNA transcription: A novel insight into T-2 toxin-induced inflammation and GH deficiency in GH3 cells

X. Liu, D. Huang, P. Guo, Q. Wu, M. Dai, G. Cheng, H. Hao, S. Xie, Z. Yuan, X. Wang,

. 2017 ; 392 (-) : 81-95. [pub] 20171025

Language English Country Ireland

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc18016254

Chronic exposure to low dose of T-2 toxin causes growth retardation and reduced body weight, resulting in economic losses. Excessive inflammatory cytokines and GH deficiency are important mechanisms that contribute to growth inhibition induced by T-2 toxin. However, the regulation of the inflammatory cytokines expecially IL-6, IL-1β, and TNF-α induced by T-2 toxin still remained unclear. The new transcription factor AKNA, belonging to AT-hook protein family, is closely associated with inflammation. However, it was unclear how AKNA regulate the expression of inflammatory cytokines, and there was no report on the role of AKNA in T-2 toxin mediated toxicity. Here, we investigated the role of AKNA in T-2 toxin-mediated inflammatory response and GH deficiency and the signal transduction pathway of AKNA. We showed that AKNA regulated by PKA/CREB and NF-κB pathway is a novel downstream molecular target in T-2 toxin-mediated inflammation and GH deficiency. T-2 toxin activates the PKA/CREB and NF-κB/p65 pathways, thereby promoting the direct binding of phospho-CREB and phospho-p65 to the AKNA promoter, thus inhibiting AKNA expression. GH and inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression were significantly downregulated after AKNA silencing. Furthermore, the expression of differential genes induced by T-2 toxin in the rat pituitary was further confirmed by acute toxicity tests in rats, which was consistent with the results in GH3 cells. By histopathological analysis, we confirmed the pituitary might be a novel direct target organ of T-2 toxin. These findings provided new insights into the significant role of AKNA in T-2 toxin-induced inflammatory response and growth inhibition.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18016254
003      
CZ-PrNML
005      
20180523104256.0
007      
ta
008      
180515s2017 ie f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.tox.2017.10.013 $2 doi
035    __
$a (PubMed)29079362
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ie
100    1_
$a Liu, Xianglian $u National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
245    10
$a PKA/CREB and NF-κB pathway regulates AKNA transcription: A novel insight into T-2 toxin-induced inflammation and GH deficiency in GH3 cells / $c X. Liu, D. Huang, P. Guo, Q. Wu, M. Dai, G. Cheng, H. Hao, S. Xie, Z. Yuan, X. Wang,
520    9_
$a Chronic exposure to low dose of T-2 toxin causes growth retardation and reduced body weight, resulting in economic losses. Excessive inflammatory cytokines and GH deficiency are important mechanisms that contribute to growth inhibition induced by T-2 toxin. However, the regulation of the inflammatory cytokines expecially IL-6, IL-1β, and TNF-α induced by T-2 toxin still remained unclear. The new transcription factor AKNA, belonging to AT-hook protein family, is closely associated with inflammation. However, it was unclear how AKNA regulate the expression of inflammatory cytokines, and there was no report on the role of AKNA in T-2 toxin mediated toxicity. Here, we investigated the role of AKNA in T-2 toxin-mediated inflammatory response and GH deficiency and the signal transduction pathway of AKNA. We showed that AKNA regulated by PKA/CREB and NF-κB pathway is a novel downstream molecular target in T-2 toxin-mediated inflammation and GH deficiency. T-2 toxin activates the PKA/CREB and NF-κB/p65 pathways, thereby promoting the direct binding of phospho-CREB and phospho-p65 to the AKNA promoter, thus inhibiting AKNA expression. GH and inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression were significantly downregulated after AKNA silencing. Furthermore, the expression of differential genes induced by T-2 toxin in the rat pituitary was further confirmed by acute toxicity tests in rats, which was consistent with the results in GH3 cells. By histopathological analysis, we confirmed the pituitary might be a novel direct target organ of T-2 toxin. These findings provided new insights into the significant role of AKNA in T-2 toxin-induced inflammatory response and growth inhibition.
650    _2
$a zvířata $7 D000818
650    _2
$a buněčné linie $7 D002460
650    _2
$a protein vázající cAMP responzivní element $x metabolismus $7 D017362
650    _2
$a proteinkinasy závislé na cyklickém AMP $x metabolismus $7 D017868
650    _2
$a DNA vazebné proteiny $x genetika $x metabolismus $7 D004268
650    _2
$a down regulace $7 D015536
650    _2
$a umlčování genů $7 D020868
650    _2
$a zánět $x chemicky indukované $x genetika $7 D007249
650    _2
$a interleukin-1beta $x genetika $x metabolismus $7 D053583
650    _2
$a interleukin-6 $x genetika $x metabolismus $7 D015850
650    _2
$a NF-kappa B $x metabolismus $7 D016328
650    _2
$a jaderné proteiny $x genetika $x metabolismus $7 D009687
650    _2
$a fosforylace $7 D010766
650    _2
$a promotorové oblasti (genetika) $7 D011401
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a T-2 toxin $x toxicita $7 D013605
650    _2
$a transkripční faktory $x genetika $x metabolismus $7 D014157
650    _2
$a TNF-alfa $x genetika $x metabolismus $7 D014409
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Huang, Deyu $u MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China.
700    1_
$a Guo, Pu $u MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China.
700    1_
$a Wu, Qinghua $u College of Life Science, Yangtze University, Jingzhou, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.
700    1_
$a Dai, Menghong $u Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
700    1_
$a Cheng, Guyue $u Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
700    1_
$a Hao, Haihong $u Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
700    1_
$a Xie, Shuyu $u Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
700    1_
$a Yuan, Zonghui $u National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
700    1_
$a Wang, Xu $u National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China. Electronic address: wangxu@mail.hzau.edu.cn.
773    0_
$w MED00004533 $t Toxicology $x 1879-3185 $g Roč. 392, č. - (2017), s. 81-95
856    41
$u https://pubmed.ncbi.nlm.nih.gov/29079362 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20180515 $b ABA008
991    __
$a 20180523104440 $b ABA008
999    __
$a ok $b bmc $g 1299878 $s 1013094
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 392 $c - $d 81-95 $e 20171025 $i 1879-3185 $m Toxicology $n Toxicology $x MED00004533
LZP    __
$a Pubmed-20180515

Find record

Citation metrics

Archiving options