Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Inhibition of extracellular signal-regulated kinase downregulates endoplasmic reticulum stress-induced apoptosis and decreases brain injury in a cardiac arrest rat model

ZL. Yuan, ZX. Zhang, YZ. Mo, DL. Li, L. Xie, MH. Chen

. 2022 ; 71 (3) : 413-423. [pub] 20220526

Jazyk angličtina Země Česko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22021452

Cerebral ischemia-reperfusion injury (CIRI) is the predominant cause of neurological disability after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The endoplasmic reticulum stress (ERs)-induced apoptosis plays an important role in neuronal survival/death in CIRI. Our previous studies reported that the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, alleviates CIRI after CA/CPR. Whether ERs-induced apoptosis is involved in the neuroprotection of PD98059 remains unknown. This study aims to investigate the effects of ERK inhibition by PD98059 on ERs-induced apoptosis after CIRI in the CA/CPR rat model. The baseline characteristics of male adult Sprague-Dawley (SD) rats in all groups were evaluated before CA/CPR. The SD rats that survived from CA/CPR were randomly divided into 3 groups (n=12/group): normal saline group (1 ml/kg), dimethylsulfoxide (DMSO, the solvent of PD98059, 1 ml/kg) group, PD98059 group (0.3 mg/kg). Another 12 SD rats were randomly selected as the Sham group. Twenty-four hours after resuscitation, neural injury was assessed by survival rate, neurological deficit scores (NDS) and Nissl staining; apoptosis of brain cells was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; mRNA expression and protein levels of ERs-related protein BIP, PERK, ATF4 and CHOP were checked with RT-PCR and Western Blot. The results showed that there were no significant differences in baseline characteristics before CA/CPR among all groups. PD98059 significantly improved survival rate and NDS, increased the Nissl bodies in neurons, reduced apoptosis, downregulated the mRNA transcription and expression levels of BIP, PERK, ATF4 and CHOP at 24 h after CA/CPR. Our results demonstrate that inhibition of ERK by PD98059 alleviates ERs-induced apoptosis via BIP-PERK-ATF4-CHOP signaling pathway and mitigates CIRI in the CA/CPR rat model.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22021452
003      
CZ-PrNML
005      
20230517085609.0
007      
ta
008      
220907s2022 xr ad f 000 0|eng||
009      
AR
024    7_
$a 10.33549/physiolres.934882 $2 doi
035    __
$a (PubMed)35616042
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xr
100    1_
$a Yuan, Zhang-Li $u Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
245    10
$a Inhibition of extracellular signal-regulated kinase downregulates endoplasmic reticulum stress-induced apoptosis and decreases brain injury in a cardiac arrest rat model / $c ZL. Yuan, ZX. Zhang, YZ. Mo, DL. Li, L. Xie, MH. Chen
520    9_
$a Cerebral ischemia-reperfusion injury (CIRI) is the predominant cause of neurological disability after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The endoplasmic reticulum stress (ERs)-induced apoptosis plays an important role in neuronal survival/death in CIRI. Our previous studies reported that the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, alleviates CIRI after CA/CPR. Whether ERs-induced apoptosis is involved in the neuroprotection of PD98059 remains unknown. This study aims to investigate the effects of ERK inhibition by PD98059 on ERs-induced apoptosis after CIRI in the CA/CPR rat model. The baseline characteristics of male adult Sprague-Dawley (SD) rats in all groups were evaluated before CA/CPR. The SD rats that survived from CA/CPR were randomly divided into 3 groups (n=12/group): normal saline group (1 ml/kg), dimethylsulfoxide (DMSO, the solvent of PD98059, 1 ml/kg) group, PD98059 group (0.3 mg/kg). Another 12 SD rats were randomly selected as the Sham group. Twenty-four hours after resuscitation, neural injury was assessed by survival rate, neurological deficit scores (NDS) and Nissl staining; apoptosis of brain cells was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; mRNA expression and protein levels of ERs-related protein BIP, PERK, ATF4 and CHOP were checked with RT-PCR and Western Blot. The results showed that there were no significant differences in baseline characteristics before CA/CPR among all groups. PD98059 significantly improved survival rate and NDS, increased the Nissl bodies in neurons, reduced apoptosis, downregulated the mRNA transcription and expression levels of BIP, PERK, ATF4 and CHOP at 24 h after CA/CPR. Our results demonstrate that inhibition of ERK by PD98059 alleviates ERs-induced apoptosis via BIP-PERK-ATF4-CHOP signaling pathway and mitigates CIRI in the CA/CPR rat model.
650    _2
$a zvířata $7 D000818
650    _2
$a apoptóza $7 D017209
650    12
$a poranění mozku $7 D001930
650    _2
$a stres endoplazmatického retikula $7 D059865
650    _2
$a extracelulárním signálem regulované MAP kinasy $7 D048049
650    12
$a srdeční zástava $x komplikace $7 D006323
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a messenger RNA $7 D012333
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a potkani Sprague-Dawley $7 D017207
650    12
$a reperfuzní poškození $x metabolismus $7 D015427
655    _2
$a časopisecké články $7 D016428
700    1_
$a Zhang, Zong-Xiang $u Intensive Care Unit, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
700    1_
$a Mo, Yan-Zi $u Intensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
700    1_
$a Li, De-Li $u Intensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
700    1_
$a Xie, Lu $u Department of Physiology, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
700    1_
$a Chen, Meng-Hua $u Intensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
773    0_
$w MED00003824 $t Physiological research $x 1802-9973 $g Roč. 71, č. 3 (2022), s. 413-423
856    41
$u https://pubmed.ncbi.nlm.nih.gov/35616042 $y Pubmed
910    __
$a ABA008 $b A 4120 $c 266 $y p $z 0
990    __
$a 20220907 $b ABA008
991    __
$a 20230517085605 $b ABA008
999    __
$a ok $b bmc $g 1851682 $s 1172720
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 71 $c 3 $d 413-423 $e 20220526 $i 1802-9973 $m Physiological research $n Physiol. Res. (Print) $x MED00003824
LZP    __
$b NLK198 $a Pubmed-20220907

Najít záznam

Citační ukazatele

Možnosti archivace