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Increased brain synthesis of prostaglandin E-2 and F-2-isoprostane in human and experimental transmissible spongiform encephalopathies

Increased brain synthesis of prostaglandin E-2 and F-2-isoprostane in human and experimental transmissible spongiform encephalopathies
Increased brain synthesis of prostaglandin E-2 and F-2-isoprostane in human and experimental transmissible spongiform encephalopathies
The levels of 2 arachidonic acid metabolites formed either by enzymatic activity of cyclooxygenase, i.e. prostaglandin E2 (PGE2), or by free radical-catalyzed peroxidation, i.e. F2-isoprostane 8-epi-prostaglandin F2[alpha] (8-epi-PGF2[alpha]), were measured in the CSF of subjects with sporadic and familial Creutzfeldt-Jakob disease (CJD) and in brain homogenates of scrapie-infected mice. The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders. Similarly, PGE2 and 8-epi-PGF2[alpha] levels were higher in brain homogenates obtained from C57BL/6J mice infected with the ME7 scrapie strain than in brain homogenates from control animals. As PGE2 is 1 of the most abundant prostaglandins released during inflammation and 8-epi-PGF2[alpha] is a quantitative marker of lipid peroxidation, our results provide in vivo biochemical evidence for the occurrence of inflammation and oxidative stress in human and experimental transmissible spongiform encephalopathies (TSEs), a concept so far based mainly on histopathological and in vitro evidence. Interestingly, in sporadic CJD patients, high CSF levels of PGE2, but not 8-epi-PGF2[alpha], correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease.
0022-3069
866-871
Minghetti, L.
e5837f6e-d84f-4f4a-af54-fdf9c664e80b
Greco, A.
f27958bc-9fe8-4ceb-b6ed-178bae346af8
Cardone, F.
31c29ad9-96db-476a-9270-75ee3cab6e45
Puopolo, M.
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Ladogana, A.
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Almonti, S.
c363fdff-84e9-4ec1-a429-ccab6e5f7787
Cunningham, C.
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Perry, V.H.
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Pocchiari, M.
9fe7f9b7-77b2-4f15-98af-08d23f8d1bbb
Levi, G.
e1b01aa1-fe92-4302-8cb4-20bc9f55b483
Minghetti, L.
e5837f6e-d84f-4f4a-af54-fdf9c664e80b
Greco, A.
f27958bc-9fe8-4ceb-b6ed-178bae346af8
Cardone, F.
31c29ad9-96db-476a-9270-75ee3cab6e45
Puopolo, M.
9640c6ee-d199-4799-8dc6-15a6530dcfb2
Ladogana, A.
5f678327-bffc-4686-b544-662a8c28dbc3
Almonti, S.
c363fdff-84e9-4ec1-a429-ccab6e5f7787
Cunningham, C.
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Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Pocchiari, M.
9fe7f9b7-77b2-4f15-98af-08d23f8d1bbb
Levi, G.
e1b01aa1-fe92-4302-8cb4-20bc9f55b483

Minghetti, L., Greco, A., Cardone, F., Puopolo, M., Ladogana, A., Almonti, S., Cunningham, C., Perry, V.H., Pocchiari, M. and Levi, G. (2000) Increased brain synthesis of prostaglandin E-2 and F-2-isoprostane in human and experimental transmissible spongiform encephalopathies. Journal of Neuropathology & Experimental Neurology, 59 (10), 866-871.

Record type: Article

Abstract

The levels of 2 arachidonic acid metabolites formed either by enzymatic activity of cyclooxygenase, i.e. prostaglandin E2 (PGE2), or by free radical-catalyzed peroxidation, i.e. F2-isoprostane 8-epi-prostaglandin F2[alpha] (8-epi-PGF2[alpha]), were measured in the CSF of subjects with sporadic and familial Creutzfeldt-Jakob disease (CJD) and in brain homogenates of scrapie-infected mice. The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders. Similarly, PGE2 and 8-epi-PGF2[alpha] levels were higher in brain homogenates obtained from C57BL/6J mice infected with the ME7 scrapie strain than in brain homogenates from control animals. As PGE2 is 1 of the most abundant prostaglandins released during inflammation and 8-epi-PGF2[alpha] is a quantitative marker of lipid peroxidation, our results provide in vivo biochemical evidence for the occurrence of inflammation and oxidative stress in human and experimental transmissible spongiform encephalopathies (TSEs), a concept so far based mainly on histopathological and in vitro evidence. Interestingly, in sporadic CJD patients, high CSF levels of PGE2, but not 8-epi-PGF2[alpha], correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease.

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Published date: October 2000
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 56741
URI: http://eprints.soton.ac.uk/id/eprint/56741
ISSN: 0022-3069
PURE UUID: 709ad14b-6b7b-4cc4-8cec-8d0711c842e0

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Date deposited: 22 Aug 2008
Last modified: 22 Jul 2022 21:07

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Contributors

Author: L. Minghetti
Author: A. Greco
Author: F. Cardone
Author: M. Puopolo
Author: A. Ladogana
Author: S. Almonti
Author: C. Cunningham
Author: V.H. Perry
Author: M. Pocchiari
Author: G. Levi

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