scholarly journals Prothrombin Kringle-2: A Potential Inflammatory Pathogen in the Parkinsonian Dopaminergic System

2016 ◽  
Vol 25 (4) ◽  
pp. 147-155 ◽  
Author(s):  
Eunju Leem ◽  
Kyoung Hoon Jeong ◽  
So-Yoon Won ◽  
Won-Ho Shin ◽  
Sang Ryong Kim
Keyword(s):  
Dopaminergic System ◽  
Kringle 2

Effects of Silibinin Against Prothrombin Kringle-2-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System In Vivo

2019 ◽  
Vol 22 (3) ◽  
pp. 277-285 ◽  
Author(s):  
Eunju Leem ◽  
Yong-Seok Oh ◽  
Won-Ho Shin ◽  
Byung Kwan Jin ◽  
Jae Yeong Jeong ◽  
...  
Keyword(s):  
Dopaminergic System ◽  
Kringle 2

Properties of Chimeric (Tissue-Type/Urokinase-Type) Plasminogen Activators Obtained by Fusion at the Plasmin Cleavage Site

1993 ◽  
Vol 69 (05) ◽  
pp. 466-472 ◽  
Author(s):  
M Colucci ◽  
L G Cavallo ◽  
G Agnelli ◽  
A Mele ◽  
R Bürgi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Cleavage Site ◽  
Plasminogen Activators ◽  
Tissue Type ◽  
Low Molecular Weight ◽  
Single Chain ◽  
Type Plasminogen Activator ◽  
Kringle 2 ◽  
Fibrin Monomers

SummaryTwo hybrid plasminogen activators (K2tu-PA and FK2tu-PA), linking the kringle 2 domain or the finger plus the kringle 2 domains of tissue-type plasminogen activator (t-PA) to the catalytic domain of single-chain urokinase-type plasminogen activator (scu-PA) were studied. At variance with similar constructs previously reported, they were obtained by fusion of the t-PA and scu-PA derived portions at their plasmin cleavage site (between Arg275 of t-PA and Ile159 of scu-PA), thus eliminating from scu-PA the two peptide bonds (Glu143-Leu144 and Arg156-Phe157) that lead to low molecular weight scu-PA and to thrombin-inactivated tcu-PA. The specific activities of K2tu-PA and FK2tu-PA, as measured by fibrin plate were 2.5 × 106 and 1.0 × 106 t-PA equivalent units/mg, respectively. Activation of plasminogen by hybrid PAs was stimulated by both CNBr-digested fibrinogen (40- and 80-fold) and Des-A-fibrin monomers (6- and 12-fold). The relatively weak stimulation of chimeric PAs by minimally degraded fibrin monomers was consistent with their reduced fibrin binding capacity. Like scu-PA, the chimeric PAs, in the single-chain form, were insensitive to inhibition, as they retained full activity after prolonged incubation in plasma and did not interact with SDS-reactivated recombinant PAI-1. The concentration producing 50% lysis of blood clots in 3 h was 0.5 μg/ml for K2tu-PA and 1 μg/ml for FK2tu-PA, as compared to 0.5 μg/ml and >2 μg/ml for t-PA and scu-PA, respectively. Plasminogen and α2-antiplasmin consumption induced by the hybrid PAs in clot-free plasma was comparable to (K2tu-PA) or lower than (FK2tu-PA) that induced by either t-PA or scu-PA. When exposed to plasmin, the hybrids were completely converted into two-chain molecules with full enzymatic activity. At variance with u-PA, however, the two-chain recombinant activators still required fibrin for full expression of activity. These data indicate that the products of such “artificial” fusion behave like true chimeras without loss of biological activity. The insensitivity to thrombin inactivation and to the proteolytic cleavage leading to low molecular weight scu-PA might confer enhanced stability to the molecules, especially at thrombus level. Moreover, if the thrombolytic activity observed in vitro is maintained in vivo, the prolonged half life of these hybrids should result in higher plasma levels of activator and thus in more extensive and rapid lysis.

Aripiprazole has both agonistic and antagonistic effects on the dopaminergic system in endocrinological challenge tests

2007 ◽  
Vol 40 (05) ◽  
Author(s):  
C Schüle ◽  
AK Schmidt ◽  
TC Baghai ◽  
D Eser ◽  
S Wenninger ◽  
...  
Keyword(s):  
Dopaminergic System ◽  
Antagonistic Effects ◽  
Challenge Tests

Method for prediction of development of neurodegenerative diseases withgamma-sinuclein dysfunction using pressure measurement after ocularinstallations of dopaminergic system on the intraocular pressure

2020 ◽  
pp. 78-79
Author(s):  
V.S. Ogorodnik ◽  
◽  
T.A. Pavlenko ◽  
A.V. Grigoryev ◽  
O.V. Beznos ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Neurodegenerative Diseases ◽  
Pressure Measurement ◽  
Dopaminergic System

Актуальность. Патологическая агрегация γ-синуклеина, одного из членов семейства синуклеинов, ассоциирована не только с болезнью Паркинсона, боковым амиотрофическим склерозом, но и с развитием глаукомы. Данный белок, являясь синаптическим, участвует в процессе везикулярного транспорта и высвобождении медиаторов, в частности дофамина. Цель. Обоснование возможности прогнозирования нарушения функции γ-синуклеина по влиянию регуляторов дофаминергической системы на уровень ВГД. Материал и методы. У 15 мышей (30 глаз) синактивированным геном, кодирующим γ-синуклеин (γ-KO) из лаборатории V. Buchman (TheJackson Laboratory – B6.129P2-Sncgtm1Vlb/J и008843) и у 20 контрольных мышей дикого типа (40глаз) того же возраста (2,5-3,5 месяцев) проводили измерение внутриглазного давления (ВГД) до и после однократной инстилляции по 10 мкл в оба глазарегуляторов дофаминергической системы (мелатонина 0,1%, Галоперидола 0,2%, дофамина 10%).Мышам проводили измерение ВГД через каждые30 минут в течение двух часов. Для каждого препарата-регулятора формировалась отдельная группа мышей. Результаты. У мышей γ-KO выявлено снижение ВГД в течение 2 часов более, чем на 4-5 ммрт. ст в ответ на инстилляцию мелатонина 0,1%(р<0,03), Галоперидола 0,2% (р<0,03) и дофамина10% (р<0,03) по сравнению с мышами дикого типа, где наблюдалось незначительное снижение уровня ВГД соответствующих регуляторов. Выводы. Предложенный способ измерения ВГД после инстилляции препаратов, влияющих на метаболизм дофамина, позволяет выявлять и прогнозировать развитие недостаточности функции γ-синуклеина и его влияние на регуляцию ВГД и формировать группы риска для динамического наблюдения и выбора превентивных лечебных мероприятий.

Targeting Dopaminergic System for Treating Nicotine Dependence

2016 ◽  
Vol 16 (2) ◽  
pp. 137-142
Author(s):  
Sawsan Abuhamdah ◽  
Ashraf Khalil ◽  
Youssef Sari
Keyword(s):  
Nicotine Dependence ◽  
Dopaminergic System
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