Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath.

Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath. Research Abstract Details 

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Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath. Abstract Text:

Tama Evron,Brian C Geyer,Irene Cherni,Mrinalini Muralidharan,Jacquelyn Kilbourne,Samuel P Fletcher,Hermona Soreq,Tsafrir S Mor,

Therapeutically valuable proteins are often rare and/or unstable in their natural context, calling for production solutions in heterologous systems. A relevant example is that of the stress-induced, normally rare, and naturally unstable "read-through" human acetylcholinesterase variant, AChE-R. AChE-R shares its active site with the synaptic AChE-S variant, which is the target of poisonous organophosphate anticholinesterase insecticides such as the parathion metabolite paraoxon. Inherent AChE-R overproduction under organophosphate intoxication confers both short-term protection (as a bioscavenger) and long-term neuromuscular damages (as a regulator). Here we report the purification, characterization, and testing of human, endoplasmic reticulum-retained AChE-R(ER) produced from plant-optimized cDNA in Nicotiana benthamiana plants. AChE-R(ER) purified to homogeneity showed indistinguishable biochemical properties, with IC50 = 10(-7) M for the organophosphate paraoxon, similar to mammalian cell culture-derived AChE. In vivo titration showed dose-dependent protection by intravenously injected AChE-R(ER) of FVB/N male mice challenged with a lethal dose of paraoxon, with complete elimination of short-term clinical symptoms at near molar equivalence. By 10 days postexposure, AChE-R prophylaxis markedly limited postexposure increases in plasma murine AChE-R levels while minimizing the organophosphate-induced neuromuscular junction dismorphology. Our findings present plant-produced AChE-R(ER) as a bimodal agent, conferring both short- and long-term protection from organophosphate intoxication.

Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath. Publishing Authors By Initials

T Evron,BC Geyer,I Cherni,M Muralidharan,J Kilbourne,SP Fletcher,H Soreq,TS Mor,

For similar plants: plant families and groups: angiosperms: solanaceae: tobacco research abstracts see: plants: plant families and groups: angiosperms: solanaceae: tobacco research

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Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The FASEB journal : official publication of the Fe

VOLUME: 21

Page Numbers: 2961-9

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 2

MONTH: 05

YEAR: 2007

Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8804484

Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath. Keywords Mesh Terms:

KEYWORDS: Tobacco

MESH TERMS: genetics

Chemical & Substance for Abstract: Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath. Information

Substance Name: Acetylcholinesterase

Registry Number: EC 3.1.1.7

Grant and Affiliation Information for Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath.

AFFILIATION: School of Life Sciences and Biodesign Inst, P.O. Box 874501, Arizona State University, Tempe, AZ 85287-4501, USA.

Country: United States

AGENCY: United States PHS

GRANT: U54N5058183-01

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MEDLINETA: FASEB J

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