Recombinant Protein Production of Earthworm Lumbrokinase for Potential Antithrombotic Application

Wang, Kevin Yueju; Tull, Lauren; Cooper, Edwin L.; Wang, Nan; Liu, Dehu

doi:10.1155/2013/783971

Cited by 30 publications

(26 citation statements)

References 38 publications

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“…LK is a fibrinolytic enzyme originated from earthworm which has shown to possess antithrombotic action (Wang et al 2013). The micelles consisted of a block copolymer of polycaprolactone-b-poly(2-(dimethylamino) ethyl methacrylate) (PCL-PDMAEMA), as well as a block copolymer of methoxy polyethylene glycol-b-polycaprolactone (mPEG-PCL) missed with a block copolymer of polycaprolactone-b-polyethylene glycol with an RGD peptide conjugated (PCL-PEG-RGDfk) forming a treatment known as LKTM (Pan et al 2018).…”

Section: Micellesmentioning

confidence: 99%

The use of nanotechnology in cardiovascular disease

2018

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Cardiovascular diseases claim a number of lives globally; many of which are preventable. With the increase in diets that consist of high saturated fat, salt, and sugar, people often living sedentary lifestyles, and a rise in cases of obesity, the incidence of cardiovascular disease is increasing. These contributing factors, coupled with more advanced methods of diagnosis, have delivered statistics that clearly show that there is a rising trend in the prevalence of cardiovascular disease. Treatment for cardiovascular diseases is limited currently to oral medicines or invasive surgery. There is a huge gap in this area of medicine for novel therapeutics for improved patient outcomes. Nanotechnology may provide a solution to more effective treatment of disease, with better prognoses and a reduced side effect profile. This review will explore for potential solutions to the limited pharmacological therapies currently on the market and the future that lies ahead for the place of nanotechnology within cardiovascular medicine.

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Section: Micellesmentioning

confidence: 99%

The use of nanotechnology in cardiovascular disease

2018

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“…The molecular weights of LK proteins are in the range of 20 to 40 kDa and their isoelectric points (pI) are about 3 to 5. Since prokaryotic cells are not capable of performing post‐translational modifications, Escherichia coli was not suggested to express eukaryotic LK proteins with proper folding, processing, and glycosylation . Studies have shown that LK proteins contain glycan chains .…”

Section: Introductionmentioning

confidence: 99%

“…There is an increasing demand for LK protein for the development of various applications of LK in the treatment of thrombotic and vascular disease therapies. LK is also considered a very good candidate for recombinant production in a plant expression system . Unlike most proteins, LK proteins can be absorbed in the gastrointestinal tract intact and retain activity .…”

Section: Introductionmentioning

confidence: 99%

“…Since prokaryotic cells are not capable of performing post-translational modifications, Escherichia coli was not suggested to express eukaryotic LK proteins with proper folding, processing, and glycosylation. 8 Studies have shown that LK proteins contain glycan chains. 9 Wu et al isolated eight LK proteins from E. fetida.…”

Section: Introductionmentioning

confidence: 99%

“…LK is also considered a very good candidate for recombinant production in a plant expression system. 8 Unlike most proteins, LK proteins can be absorbed in the gastrointestinal tract intact and retain activity. 3 Therefore, in a plant expression system, LK proteins could be expressed in a vegetable, fruit or edible seed and consumed as pharmaceutical agent directly as food, which would eliminate the need for extraction and purification.…”

Section: Introductionmentioning

confidence: 99%

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Expression of cholera toxin B subunit–lumbrokinase in edible sunflower seeds–the use of transmucosal carrier to enhance its fusion protein's effect on protection of rats and mice against thrombosis

Guan

Chen

et al. 2014

Biotechnology Progress

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Lumbrokinase (LK) is a group of serine proteases with strong fibrinolytic and thrombolytic activities and is useful for treating diseases caused by thrombus. Cholera toxin B subunit (CTB) has been widely used to facilitate antigen delivery by serving as an effective mucosal carrier molecule for the induction of oral tolerance. We investigate here the application of CTB as a transmucosal carrier in enhancing its fusion protein-LKs effect to protect rats against thrombosis. Thus, in this study, CTB-LK fusion gene separated by a furin cleavage site was expressed in seeds of Helianthus annuus L. The activity of recombinant protein in seeds of transgenic sunflower was confirmed by Western blot analysis, fibrin plate assays and GM1 -ganglioside ELISA. The thrombosis model of rats and mice revealed that the oral administration of peeled seeds of sunflower expressing CTB-LK had a more significant anti-thrombotic effect on animals compared with that administration of peeled seeds of sunflower expressing LK. It is possible to conclude that CTB can successfully enhance its fusion protein to be absorbed in rats or mice thrombosis model. The use of CTB as a transmucosal carrier in the delivery of transgenic plant-derived oral therapeutic proteins was supported. In addition, for the purpose of that recombinant CTB-LK was designed for oral administration, thus the expression of CTB-LK in edible sunflower seeds eliminated the need for downstream processing of proteins.

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Potential clinical applications of phytopharmaceuticals for the in‐patient management of coagulopathies in COVID‐19

Mukherjee

Chattopadhyay

2022

Phytotherapy Research

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Thrombotic complications occur in many cardiovascular pathologies and have been demonstrated in COVID‐19. The currently used antithrombotic drugs are not free of adverse reactions, and COVID‐19 patients in particular, when treated with a therapeutic dose of an anticoagulant do not receive mortality benefits. The clinical management of COVID‐19 is one of the most difficult tasks for clinicians, and the search for safe, potent, and effective antithrombotic drugs may benefit from exploring naturally bioactive molecules from plant sources. This review describes recent advances in understanding the antithrombotic potential of herbal drug prototypes and points to their future clinical use as potent antithrombotic drugs. Although natural products are perceived to be safe, their clinical and therapeutic applications are not always apparent or accepted. More in‐depth studies are necessary to demonstrate the clinical usefulness of plant‐derived, bioactive compounds. In addition, holistic approaches in systematic investigations and the identification of antithrombotic mechanisms of the herbal bioactive molecule(s) need to be conducted in pre‐clinical studies. Moreover, rigorous studies are needed to compare the potency of herbal drugs to that of competitor chemical antithrombotic drugs, and to examine their interactions with Western antithrombotic medicines. We have also proposed a road map to improve the commercialization of phytopharmaceuticals.

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Recombinant Protein Production of Earthworm Lumbrokinase for Potential Antithrombotic Application

Cited by 30 publications

References 38 publications

The use of nanotechnology in cardiovascular disease

The use of nanotechnology in cardiovascular disease

Expression of cholera toxin B subunit–lumbrokinase in edible sunflower seeds–the use of transmucosal carrier to enhance its fusion protein's effect on protection of rats and mice against thrombosis

Potential clinical applications of phytopharmaceuticals for the in‐patient management of coagulopathies in COVID‐19

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