Proteomic approach with LCMS-IT-TOF identified an increase of Rab33B after transient focal cerebral ischemia in mice

Abstract Background Several proteins are known to be markedly expressed in the brain during cerebral ischemia; however, the changes in protein profiles within the ischemic brain after an ischemic insult have not been fully elucidated. We studied the changes in the ischemic brain proteome after focal cerebral ischemia, induced by middle cerebral artery occlusion (MCAO) in mice. Methods LCMS-IT-TOF mass spectrometry was used to detect the changes in ischemic brain protein patterns after MCAO. We evaluated the protein expression detected in the ischemic area, by western blotting and immunohistochemistry. Results Nine unique proteins were identified from the ischemic area at 10 h after ischemic insult. Among these proteins, we focused on Rab33b, a member of RAS oncogene family and we found that Rab33b was up-regulated in the ischemic striatum and the number of Rab33B-positive cells increased in a time-dependent manner. Rab33B colocalized with Iba-1 positive microglia in the ischemic area. Conclusion These findings suggest that LCMS-IT-TOF is useful for identifying changes in proteins after cerebral ischemia and that Rab33B is partially related to the pathogenesis of transient cerebral ischemia in mice. </jats:sec

チュウカ ノ ケイセイ ト トウホウ セカイ キヨナガ ショウジ センセイ ニッタ ヒデハル センセイ タイニン キネンゴウ

講演(Lecture

シン シコウテイ チョウジョウ デンセツ ト ソノ ブタイ シン ケッセキキュウ ト モウキョウジョ デンセツ オ ツナグ モノ デントウ チュウゴク ノ セイジ リネン トシハイ

To　the　northwest　of　the　city　of　Qinhuangdao秦皇島in　Heibei Province，　in　Wangfushi望夫石Village　on　the　provincial　border　with Liaoning遼寧stands　the　mausoleum　of　MengjiangnU孟姜女． According　to　the　legend，　MengjiangnU　is　a　tragic　heroine　who　lived during　the　early　days　of　the　Qin　Dynasty．　Soon　after　marriage　her husband　was　conscripted　to　work　in　the　construction　of　the　Great Wall．　Concerned　about　his　welfare，　she　followed　him　to　the　construction 　site　and　found　that　he　had　been　killed　in　a　cave－in．　While she　wept，　they　found　her　husband’s　remains　in　the　rubble，　and　she then　returned　home　with　the　body．　However，　MengjiangnU’s　mausoleum 　is　actually　situated　on　the　site　of　the　Ming　period　Great　Wal1， while　the　Qin　period　Great　Wall　is　located　much　farther　north，　clearly indicating　that　the　legend　is　not　from　the　Qin　period．　Indeed，　legends of　later　eras　not　directly　connected　with　the　Qin　period　are　not　very helpful　as　historical　source　materials　for　its　study；however，　the situation　changed　greatly　when　in　19820n　the　seashore　across　the water　from　the　Jiangnushi姜女石the　remains　of　a　large　cluster　of remote　palaces　from　the　Qin　and　Han　periods　were　unearthed．　The purpose　of　the　present　article　is　to　trace　more　systematically　the development　from　the　Great　Wall　legend　to　the　MengjiangnU　legend in　an　attempt　to　discover　historical　facts　about　the　Qin　period　from folklore　of　a　later　era． 　　The　investigation　reveals　that　the　development　of　such　Great　Wall folklore　as　the　MengjiangnU　legend　is　connected　to　confusion　concerning 　historical　sites　that　from　its　setting　in　the　Jieshi　ma石peaks on　the　Bohai　seacoast．　That　is　to　say，　Iegends　lamenting　the　hardships 　and　casualties　suffered　by　the　anonymous　masses　who　built　the Great　Wall　were　originally　derived　from　tales　of　the　wives　of　Qiliang 杞梁who　lost　their　husbands　in　battle．　The　author　estimates　that the　change　of　setting　from　the　battlefield　to　the　Great　Wall　and　the creation　of　the　MengjiangnU　legend　took　place　in　pre－Tang　China during　the　latter　part　of　Wei　and　Jin　eras　of　the　Northern　and Southern　Dynasties　period．　Furthermore，　the　geographical　location for　the　new　Iegend，　Yuwang禺王site　in　the　Jieshi　peaks　on　the　Bohai seacoast，　despite　being　a　cluster　of　remote　palaces　completely　unrelated 　to　the　Great　Wall　built　during　the　Qin　and　Han　periods，　is situated　on　the　eastern　edge　of　the　Great　Wall　of　the　Northern　Qi Dynasty　of　the　Wei　and　Jin　eras　of　the　Northern　and　Southern Dynasties　period．　Jieshimen碍石門，　formed　by　two　rock　shoals　on the　Bohai　Coast，　was　inscribed　as　a　monument　to　the　first　Qin emperor，　but　was　later　destroyed　on　purpose　probably　as　an　act　of rebellion　against　the　emperor．　During　the　Wei　and　Jin　eras　of　the Northern　and　Southern　Dynasties　period，　the　original　Jieshi　peaks， from　which　residents　of　the　remote　palaces　high　above　the　coast could　look　out　on　the　mystical　eastern　sea，　were　forgotten，　and replaced　by　towering　inland　Jiehi　peaks　climbed　by　emperors　of　the Northern　Wei，　Northern　Qi，　and　Tang　Dynasties　to　view　the　eastern sea．　It　was　in　this　way　that　the　Mengjiangnu　mausoleum　and　JiangnUshi 　came　to　be　located　on　the　Bohai　Coast　with　no　relation　what so　ever　to　the　original　Jieshi　palaces　of　the　Qin　period．　Nevertheless， 　a　historical　setting　forgotten　in　the　historical　record　has　been revived　by　the　archeological　excavation　of　the　Qin　and　Han　period Jieshi　palaces　on　the　Bohai　Coast

Neutrophils-A key component of ischemia-reperfusion injury

Ischemia-reperfusion injury (IRI) is a common occurrence following myocardial infarction, transplantation, stroke, and trauma that can lead to multiple organ failure, which remains the foremost cause of death in critically ill patients. Current therapeutic strategies for IRI are mainly palliative, and there is an urgent requirement for a therapeutic that could prevent or reverse tissue damage caused by IRI. Neutrophils are the primary responders following ischemia and reperfusion and represent important components in the protracted inflammatory response and severity associated with IRI. Experimental studies demonstrate neutrophil infiltration at the site of ischemia and show that inducing neutropenia can protect organs from IRI. In this review, we highlight the mechanisms involved in neutrophil recruitment, activation, and adherence and how this contributes to disease severity in IRI. Inhibiting neutrophil mobilization, tissue recruitment, and ultimately neutrophil-associated activation of local and systemic inflammatory responses may have therapeutic potential in the amelioration of local and remote tissue damage following IRI. Copyrigh

シン チョウジョウ ケンセツ ト ソノ レキシテキ ハイケイ

論説(Article

ヒガシアジアカイ ノ ブンメイ オ モトメテ

講演(Lecture

キムラ ブザン ト チュウゴク ビジュツ コレクション ノ ユライ キムラ ブザン ト チュウゴク ビジュツ コレクション

学習院大学東洋文化研究所一般研究プロジェクト「木村武山と中国美術コレクション」（研究代表者 鶴間和幸（文学部教授）、2017 ～ 2018年度）の研究成

Diacylglycerol Kinase β Knockout Mice Exhibit Attention-Deficit Behavior and an Abnormal Response on Methylphenidate-Induced Hyperactivity

BACKGROUND: Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKβ is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKβ knockout (KO) mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density), hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKβ KO mice in order to investigate the function of DGKβ in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD). METHODOLOGY/PRINCIPAL FINDINGS: DGKβ KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.). In the open field test, DGKβ KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p.), but showed a similar response to an N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801 (0.3 mg/kg, i.p.), when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK), which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKβ KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKβ KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKβ has a pivotal involvement in ERK regulation in the striatum