title: Autophagic effect of programmed cell death 5 (PDCD5) after focal cerebral ischemic reperfusion injury in rats.
abstract: Former studies indicated that programmed cell death 5 (PDCD5) protein could accelerate the process of apoptosis in response to some stimuli in various kinds of cells via the intrinsic or extrinsic pathway. In this study, we aimed to demonstrate for the first time that protein level of PDCD5 are related to autophagic activity after focal ischemic brain injury in rats. One hundred and twenty-five Sprague-Dawley rats (male) were randomly divided into the following groups: Sham operated, Middle Cerebral Artery Occlusion/Reperfusion (MCAO), MCAO+Control siRNA and MCAO+PDCD5 siRNA. Outcome measurements include neurobehavioral outcomes, brain infarct volume, brain water content, BBB disruption, MRI and double fluorescence labeling. Western blot and histopathophysiological techniques were used to measure the expression of PDCD5 and some pro-autophagic proteins such as Beclin 1 and the LC3-II/LC3-I ratio. The study found that decreased PDCD5 expression via intracerebroventricular injection of PDCD5 siRNA significantly improved the neurobehavioral outcome, reduced the infarct ratio, cerebral edema and BBB disruption. These results were associated with decreased expression of Beclin 1 and the LC3-II/LC3-I ratio in the penumbra area. Rapamycin, an inducer of autophagy, partially weakened the effect of PDCD5 siRNA. In conclusion, this study suggested that PDCD5 was a key regulator of autophagy that might play an important role following MCAO injury.
authors.affiliation: Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Peking University Center for Human Disease Genomics, Beijing, China.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Key Laboratory of Stasis and Phlegm of State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Anesthesiology and Critical Care, Hospital of University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Riley
authors.affiliation: Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China. Electronic address: changmanzhou@hotmail.com.
authors.forename: Chang-Man
authors.initials: CM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D001812:Blood-Brain Barrier / Q000378:metabolism; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D020123:Sirolimus; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C000592906:PDCD5 protein, rat
keywords: Autophagy; MCAO; MRI; PDCD5; siRNA