• Je něco špatně v tomto záznamu ?

The critical role of p16/Rb pathway in the inhibition of GH3 cell cycle induced by T-2 toxin

Z. Fatima, P. Guo, D. Huang, Q. Lu, Q. Wu, M. Dai, G. Cheng, D. Peng, Y. Tao, M. Ayub, MT. Ul Qamar, MW. Ali, X. Wang, Z. Yuan,

. 2018 ; 400-401 (-) : 28-39. [pub] 20180319

Jazyk angličtina Země Irsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19012764

T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40 nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (△Ym) upon exposure to the T-2 toxin. Flow cytometry showed a significant time-dependent increase in percentage of apoptotic cells and gel electrophoresis showed the hallmark of apoptosis oligonucleosomal DNA fragmentation. Additionally, T-2 toxin-induced oxidative stress and DNA damage with a time-dependent significant increased expression of p53 favors the apoptotic process by the activation of caspase-3 in T-2 toxin treated cells. Cell cycle analysis by flow cytometry revealed a time-dependent increase ofG1 cell population along with the significant time-dependent up-regulation of mRNA and protein expression of p16 and p21 and significant down-regulation of cyclin D1, CDK4, and p-RB levels further verify the G1 phase arrest in GH3 cells. Morphology of GH3 cells by TEM clearly showed the damage and dysfunction to mitochondria and the cell nucleus. These findings for the first time demonstrate that T-2 toxin induces G1 phase cell cycle arrest by the involvement of p16/Rb pathway, along with ROS mediated oxidative stress and DNA damage with p53 and caspase cascade interaction, resulting in apoptosis in GH3 cells.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19012764
003      
CZ-PrNML
005      
20190412123036.0
007      
ta
008      
190405s2018 ie f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.tox.2018.03.006 $2 doi
035    __
$a (PubMed)29567467
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ie
100    1_
$a Fatima, Zainab $u National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University (HZAU), Wuhan, China.
245    14
$a The critical role of p16/Rb pathway in the inhibition of GH3 cell cycle induced by T-2 toxin / $c Z. Fatima, P. Guo, D. Huang, Q. Lu, Q. Wu, M. Dai, G. Cheng, D. Peng, Y. Tao, M. Ayub, MT. Ul Qamar, MW. Ali, X. Wang, Z. Yuan,
520    9_
$a T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40 nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (△Ym) upon exposure to the T-2 toxin. Flow cytometry showed a significant time-dependent increase in percentage of apoptotic cells and gel electrophoresis showed the hallmark of apoptosis oligonucleosomal DNA fragmentation. Additionally, T-2 toxin-induced oxidative stress and DNA damage with a time-dependent significant increased expression of p53 favors the apoptotic process by the activation of caspase-3 in T-2 toxin treated cells. Cell cycle analysis by flow cytometry revealed a time-dependent increase ofG1 cell population along with the significant time-dependent up-regulation of mRNA and protein expression of p16 and p21 and significant down-regulation of cyclin D1, CDK4, and p-RB levels further verify the G1 phase arrest in GH3 cells. Morphology of GH3 cells by TEM clearly showed the damage and dysfunction to mitochondria and the cell nucleus. These findings for the first time demonstrate that T-2 toxin induces G1 phase cell cycle arrest by the involvement of p16/Rb pathway, along with ROS mediated oxidative stress and DNA damage with p53 and caspase cascade interaction, resulting in apoptosis in GH3 cells.
650    _2
$a zvířata $7 D000818
650    _2
$a buněčný cyklus $x účinky léků $x fyziologie $7 D002453
650    _2
$a buněčné linie $7 D002460
650    _2
$a viabilita buněk $x účinky léků $x fyziologie $7 D002470
650    _2
$a geny p16 $x účinky léků $x fyziologie $7 D019942
650    _2
$a hypofýza $x účinky léků $x metabolismus $x ultrastruktura $7 D010902
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a retinoblastomový protein $x biosyntéza $7 D016160
650    _2
$a signální transdukce $x účinky léků $x fyziologie $7 D015398
650    _2
$a T-2 toxin $x toxicita $7 D013605
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
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 Huang, Deyu $u MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China.
700    1_
$a Lu, Qirong $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, Institute of Biomedicine, Yangtze University, Jingzhou, 434025, 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 Peng, Dapeng $u National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University (HZAU), Wuhan, China.
700    1_
$a Tao, Yanfei $u MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China.
700    1_
$a Ayub, Muhammad $u Jianghan Medical University, Wuhan, China.
700    1_
$a Ul Qamar, Muhammad Tahir $u College of Informatics, Huazhong Agricultural University (HZAU), Wuhan, China.
700    1_
$a Ali, Muhammad Waqar $u College of Plant Sciences, Huazhong Agricultural University (HZAU), Wuhan, China.
700    1_
$a Wang, Xu $u MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China. Electronic address: wangxu@mail.hzau.edu.cn.
700    1_
$a Yuan, Zonghui $u National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University (HZAU), Wuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China. Electronic address: yuan5802@mail.hzau.edu.cn.
773    0_
$w MED00004533 $t Toxicology $x 1879-3185 $g Roč. 400-401, č. - (2018), s. 28-39
856    41
$u https://pubmed.ncbi.nlm.nih.gov/29567467 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20190405 $b ABA008
991    __
$a 20190412123055 $b ABA008
999    __
$a ok $b bmc $g 1392074 $s 1051069
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 400-401 $c - $d 28-39 $e 20180319 $i 1879-3185 $m Toxicology $n Toxicology $x MED00004533
LZP    __
$a Pubmed-20190405

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace