The neuroprotective effects of Tanshinone IIA are associated with induced nuclear translocation of TORC1 and upregulated expression of TORC1, pCREB and BDNF in the acute stage of ischemic stroke.
The activation of cAMP response element binding protein (CREB) and transcription of CRE-targeted genes play critical roles in various physiological and pathological conditions. Transducers of regulated CREB activity (TORCs) represent a new family of conserved CREB coactivators that promote the activation of CRE-targeted genes. Tanshinone IIA (TSA) has been proven to protect the brain against focal ischemia injury. However, little is known regarding the underlying mechanisms. Herein, we examined the activity-dependent nuclear translocation of TORC1 (transducer of regulated CREB activity 1) and the expression of TORC1, phosphorylated CREB (pCREB) and BDNF (brain-derived neurotrophic factor) at the early time of ischemic stroke as well as after the treatment with TSA. We observed a bimodal increase in pCREB, TORC1 and BDNF protein levels and transient nuclear accumulation of TORC1 in the acute stage of ischemia. Compared with vehicle group, TSA (20mg/kg) dramatically lessened neurological deficits scores, brain water contents and infarct sizes, significantly enhanced nuclear accumulation of TORC1 and upregulated the expression of TORC1, pCREB and BDNF (P<0.05). Collectively, the present results suggest that TSA protects rat brain from pristine ischemic damage in cerebral cortex, which might be correlated with induced nuclear translocation of TORC1 and upregulated expression of TORC1, pCREB and BDNF.
Liu
Lingling
L
Department of Neurology, The Second Hospital of Hebei Medical University. Shijiazhuang, Hebei 050000, China.
Zhang
Xiangjian
X
Wang
Lina
L
Yang
Rui
R
Cui
Lili
L
Li
Min
M
Du
Wei
W
Wang
Shan
S
D045784:Abietanes; D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009483:Neuropsychological Tests; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D045784:Abietanes; D019208:Brain-Derived Neurotrophic Factor; C519510:Crtc1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D010616:Phenanthrenes; D014157:Transcription Factors; C021751:tanshinone