Mechanisms of lumbrokinase in protection of cerebral ischemia

Ji, Hongrui; Lian, Wang; Bi, Hui; Sun, Lihua; Cai, Benzhi; Wang, Yuping; Zhao, Jinlong; Du, Zhenhong

doi:10.1016/j.ejphar.2008.05.037

Cited by 48 publications

(30 citation statements)

References 22 publications

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“…The results show that the anti-ischemic activity of LrP was due to its antiplatelet activity by elevating cAMP level and attenuating the calcium release from calcium stores, the antithrombosis action due to inhibiting of ICAM-1 expression, and the antiapoptotic effect due to the activation of JAK1/STAT1 pathway [84].…”

Section: Anti-ischemiamentioning

confidence: 83%

Earthworm Protease

Pan

Zhang

2010

Applied and Environmental Soil Science

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The alimentary tract of earthworm secretes a group of proteases with a relative wide substrate specificity. In 1983, six isozymes were isolated from earthworm with fibrinolytic activities and called fibriniolytic enzymes. So far, more isozymes have been found from different earthworm species such as Lumbricus rubellus and Eisenia fetida. For convenience, the proteases are named on the basis of the earthworm species and the protein function, for instance, Eisenia fetida protease (Ef P). The proteases have the abilities not only to hydrolyze fibrin and other protein, but also activate proenzymes such as plasminogen and prothrombin. In the light of recent studies, eight of the Ef Ps contain oligosaccharides chains which are thought to support the enzyme structure. Interestingly, Ef P-II has a broader substrate specificity presenting alkaline trypsin, chymotrypsin and elastase activities, but Ef P-III-1 has a stricter specificity. The protein crystal structures show the characteristics in their specificities. Earthworm proteases have been applied in several areas such as clinical treatment of clotting diseases, anti-tumor study, environmental protection and nutritional production. The current clinical utilizations and some potential new applications of the earthworm protease will be discussed in this paper.

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Section: Anti-ischemiamentioning

confidence: 83%

Earthworm Protease

Pan

Zhang

2010

Applied and Environmental Soil Science

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“…LK in the earthworm was used to treat stroke and cardiovascular diseases (Hwan et al, 2004). In this experiment, LK was used to be positive control drug, its effects on resisting against cell damage, protecting against ischemic neuronal injury, and inhibiting intracellular calcium mobilization had been reported (Ji et al, 2008). Results showed there was no remarkably change between NK (9.4 mg/d and 4.7 mg/d) and LK.…”

Section: Nk Cumulative Concentration G/lmentioning

confidence: 92%

Mechanisms of Nattokinase in protection of cerebral ischemia

Liang

Liu³

et al. 2014

European Journal of Pharmacology

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In vivo, the level of cyclic Adenosine Monophosphate (cAMP) and the pathway of the Janus Kinase1/Signal Transducers and Activators of Transcription1 (JAK1/STAT1) were studied. In vitro, the Ca(2+) mobilization in human platelet stimulated by thrombin was observed. In addition, vasomotion of vascular smooth muscle was measured by adding KCl or norepinephrine(NE) under the Ca(2+) contained bath solutions. The effect induced by NE in the presence of N-nitro-L-arginine methyl ester (L-NAME) or indometacin (Indo) was also detected. At last, the levels of tissue plasminogen activator (t-PA) and Plasminogen activator inhibitor-1 (PAI-1) in cultured supernatans in Human umbilical vein endothelial cells (Huvecs) were measured by means of ELISA kit. Results showed that Nattokinase (NK) significantly increased the cAMP level, activated the signal passage of JAK1/STAT1 in injured part and inhibited remarkably the rise of platelet intracellular Ca(2+) ([Ca(2+)]i) in human platelet. Furthermore, NK relaxed rat thoracic aortic artery in the dose-dependent manner and in the endothelium dependent manner and its effect could be attenuated by L-NAME. Also, the secretion of t-PA and PAI-1 were reduced stimulated by Adr on Huvecs. These data indicated that the neuroprotective effect of NK was associated with its antiplatelet activity by elevating cAMP level and attenuating the calcium release from calcium stores; with its anti-apoptotic effect through the activation of JAK1/STAT1 pathway; with its relaxing vascular smooth muscle by promoting synthesis and release of NO, reducing ROC calcium ion influx and with its protection on endothelial cells through increasing fibrinolytic activity and facilitating spontaneous thrombolysis.

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“…The neurological deficits were tested by single blind method after MCAO, which was previously developed [16] and the evaluation of neurological deficits can be made by counting cumulative scales from scale 0 to 4, representing no visible neurological deficits as the scale 0, forelimb flexion as the scale 1, contralateral forelimb grips weakly as the scale 2, circling to the paretic side only when pulled by the tail (the animal was allowed to move about freely) as the scale 3, and spontaneous circling as the scale 4, respectively. For identification of the cerebral infarction, the brain was then removed carefully and dissected into coronal 2-mm sections after the animal was tested for neurological deficits, subsequently immersed into a 2% solution of 2,3,5-triphenyltetrazolium chloride (TTC) in normal saline at 37°C for 30 min, and then fixed in 4% paraformaldehyde solution at 4°C.…”

Section: Identification Of Cerebral Infarction and Evaluation Of Neurmentioning

confidence: 99%

Cerebral Ischemia Elicits Aberration in Myocardium Contractile Function and Intracellular Calcium Handling

Sun

Wang

et al. 2010

Cell Physiol Biochem

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The mechanisms of myocardial dysfunction and calcium handling disturbance underlying cerebral ischemia remain obscure. Here we for the first time report that acute cerebral ischemia significantly increased left ventricular end diastolic pressure (LVEDP), but decreased +dP/dt, -dP/dt, and left ventricular systolic pressure (LVSP). Significant increase in either the resting or KCl-induced [Ca²⁺]_iin ventricular myocytes was also detected by scanning confocal microscopy at 2 and 24 hours after cerebral ischemia. Verapamil as a blocker of I_Ca,L, ryanodine as a specific inhibitor of RyR, thapsigargin as a highly specific inhibitor of sarco(endo)plasmic reticulum Ca²⁺-ATPase 2a (SERCA2a) and SEA0400 as a selective NCX inhibitor changed the area under the curve of averaged ratio of fluorescence (FI/F₀I) induced by KCl. Cardiac expression of Ca_v1.2 was significantly up-regulated at 2 and 24 hours after cerebral ischemia, whereas cardiac expression of SERCA2a and Na⁺-Ca²⁺ exchanger (NCX) was significantly down-regulated at the same time period after cerebral ischemia. Cardiac expression of phospholamban (PLB) was significantly elevated at 2 hours after cerebral ischemia but was restored to about normal level at 24 hours after injury. These data suggest that acute cerebral ischemia may specifically disturb cardiac function and calcium homeostasis, which are related to increase of Ca_v1.2 and decrease of through up-regulating Ca_v1.2 and PLB, down-regulating SERCA2a and NCX, subsequently leading to Ca²⁺ overload by the enhancement of Ca²⁺ influx and inhibition of intracellular Ca²⁺ extrusion and cerebral ischemia-induced myocardial dysfunction.

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Mechanisms of lumbrokinase in protection of cerebral ischemia

Cited by 48 publications

References 22 publications

Earthworm Protease

Earthworm Protease

Mechanisms of Nattokinase in protection of cerebral ischemia

Cerebral Ischemia Elicits Aberration in Myocardium Contractile Function and Intracellular Calcium Handling

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