Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.

Thiamine (Vitamin B1) is an essential vitamin that must be obtained from the diet for proper neurological function. At higher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT)-a phosphorylated derivative of thiamine-have antinociceptive effects in animals and humans, although...

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Autores principales:	Julie K Hurt, Jennifer L Coleman, Brendan J Fitzpatrick, Bonnie Taylor-Blake, Arlene S Bridges, Pirkko Vihko, Mark J Zylka
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/94a81905acde459b9e7dc4a62c01d6f9
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spelling	oai:doaj.org-article:94a81905acde459b9e7dc4a62c01d6f92021-11-18T08:10:20ZProstatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.1932-620310.1371/journal.pone.0048562https://doaj.org/article/94a81905acde459b9e7dc4a62c01d6f92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23119057/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Thiamine (Vitamin B1) is an essential vitamin that must be obtained from the diet for proper neurological function. At higher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT)-a phosphorylated derivative of thiamine-have antinociceptive effects in animals and humans, although how these compounds inhibit pain is unknown. Here, we found that Prostatic acid phosphatase (PAP, ACPP) can dephosphorylate BT in vitro, in dorsal root ganglia (DRG) neurons and in primary-afferent axon terminals in the dorsal spinal cord. The dephosphorylated product S-benzoylthiamine (S-BT) then decomposes to O-benzoylthiamine (O-BT) and to thiamine in a pH-dependent manner, independent of additional enzymes. This unique reaction mechanism reveals that BT only requires a phosphatase for conversion to thiamine. However, we found that the antinociceptive effects of BT, thiamine monophosphate (TMP) and thiamine-a compound that is not phosphorylated-were entirely dependent on PAP at the spinal level. Moreover, pharmacokinetic studies with wild-type and Pap(-/-) mice revealed that PAP is not required for the conversion of BT to thiamine in vivo. Taken together, our study highlights an obligatory role for PAP in the antinociceptive effects of thiamine and phosphorylated thiamine analogs, and suggests a novel phosphatase-independent function for PAP.Julie K HurtJennifer L ColemanBrendan J FitzpatrickBonnie Taylor-BlakeArlene S BridgesPirkko VihkoMark J ZylkaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48562 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julie K Hurt Jennifer L Coleman Brendan J Fitzpatrick Bonnie Taylor-Blake Arlene S Bridges Pirkko Vihko Mark J Zylka Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.
description	Thiamine (Vitamin B1) is an essential vitamin that must be obtained from the diet for proper neurological function. At higher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT)-a phosphorylated derivative of thiamine-have antinociceptive effects in animals and humans, although how these compounds inhibit pain is unknown. Here, we found that Prostatic acid phosphatase (PAP, ACPP) can dephosphorylate BT in vitro, in dorsal root ganglia (DRG) neurons and in primary-afferent axon terminals in the dorsal spinal cord. The dephosphorylated product S-benzoylthiamine (S-BT) then decomposes to O-benzoylthiamine (O-BT) and to thiamine in a pH-dependent manner, independent of additional enzymes. This unique reaction mechanism reveals that BT only requires a phosphatase for conversion to thiamine. However, we found that the antinociceptive effects of BT, thiamine monophosphate (TMP) and thiamine-a compound that is not phosphorylated-were entirely dependent on PAP at the spinal level. Moreover, pharmacokinetic studies with wild-type and Pap(-/-) mice revealed that PAP is not required for the conversion of BT to thiamine in vivo. Taken together, our study highlights an obligatory role for PAP in the antinociceptive effects of thiamine and phosphorylated thiamine analogs, and suggests a novel phosphatase-independent function for PAP.
format	article
author	Julie K Hurt Jennifer L Coleman Brendan J Fitzpatrick Bonnie Taylor-Blake Arlene S Bridges Pirkko Vihko Mark J Zylka
author_facet	Julie K Hurt Jennifer L Coleman Brendan J Fitzpatrick Bonnie Taylor-Blake Arlene S Bridges Pirkko Vihko Mark J Zylka
author_sort	Julie K Hurt
title	Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.
title_short	Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.
title_full	Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.
title_fullStr	Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.
title_full_unstemmed	Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.
title_sort	prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/94a81905acde459b9e7dc4a62c01d6f9
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Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.

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