DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and nuclear factor κB in rats.
Gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppresses the activation of Notch 1 signaling, which is recognized as the cell fate signaling and may participate in inflammatory processes together with NF-κB pathway that contributes to the brain damage after stroke. DAPT has important pharmacological roles in many diseases. However, little is known about the effect of DAPT on NF-κB during cerebral ischemia. This study investigated the time course expression of Notch 1 and the effects of DAPT on Notch 1 and NF-jB after MCAO. The results showed that Notch 1 signaling was up-regulated at the early stage after MCAO, DAPT down-regulated the expression of Notch 1 and NF-κB and protected brain from damage caused by MCAO. These results may indicate that the downregulation of Notch 1–NF-κB pathway after ischemia by administration of DAPT is a potential mechanism for its protection.
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantanxili, Dongcheng District, Beijing 100050, China.
Shuya
S
Li
Xiangjian
X
Zyang
Yongjun
Y
Wang
Hui
H
Ji
Yuanyuan
Y
Du
Haichao
H
Liu
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D004151:Dipeptides / Q000008:administration & dosage*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D007276:Injections, Intraventricular; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D016328:NF-kappa B; D018696:Neuroprotective Agents; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; D053829:Amyloid Precursor Protein Secretases