Baicalein attenuates caspase-independent cells death via inhibiting PARP-1 activation and AIF nuclear translocation in cerebral ischemia/reperfusion rats.
It is reported that baicalein can activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats. However, a caspase-independent mechanism initiated by poly (ADP-ribose) polymerase-1 (PARP-1) activation has been reported to make more contribution to cells death after ischemic stroke. In the present study, we established a cerebral ischemia/reperfusion (I/R) rat model through middle cerebral artery occlusion following reperfusion to investigate the mechanisms of ischemic tissue recovery following baicalein treatment. The data showed that baicalein treatment at dose of 100 mg/kg for 7 days significantly inhibited the release of cytokines, activation of PARP-1, nuclear translocation of apoptosis-inducing factor (AIF) and macrophage migration inhibitory factor (MIF) in cerebral I/R rats, therefore decreased cerebral infarct volume and neurological scores. Then, we further investigated the signal transduction mechanisms of ischemic tissue protection by baicalein in vitro. Following oxygen and glucose deprivation (OGD) in SH-SY5Y cells, the mitochondrial AIF was translocated into nucleus after 12 h. The co-immunoprecipitation analysis showed that the interaction between AIF and MIF was activated by OGD and subsequently resulted in MIF nuclear translocation. Also, the baicalein inhibited apoptosis, reduced oxidative stress, protected mitochondrial function and restored mitochondrial membrane potential in OGD cells. The results obtained from both in vivo and in vitro study demonstrated the PARP-1/AIF pathway involved in mechanisms of baicalein to protect the cerebral tissues from ischemic injury.
['Li|Wei-Han|WH|', 'Yang|Ying-Lin|YL|', 'Cheng|Xiao|X|', 'Liu|Man|M|', 'Zhang|Shan-Shan|SS|', 'Wang|Yue-Hua|YH|http://orcid.org/0000-0002-7650-6417', 'Du|Guan-Hua|GH|']
D000818:Animals D017209:Apoptosis D051033:Apoptosis Inducing Factor D001921:Brain D002545:Brain Ischemia D002316:Cardiotonic Agents D045744:Cell Line, Tumor D002467:Cell Nucleus D044950:Flavanones D005786:Gene Expression Regulation D005947:Glucose D008297:Male D009474:Neurons D010100:Oxygen D000071137:Poly (ADP-Ribose) Polymerase-1 D021381:Protein Transport D051381:Rats D017207:Rats, Sprague-Dawley D015427:Reperfusion Injury D015398:Signal Transduction
PARP-1 activation AIF nuclear translocation Parthanatos Programed cells death