Peptide from Sea Anemone Metridium senile Affects Transient Receptor Potential Ankyrin-repeat 1 (TRPA1) Function and Produces Analgesic Effect

The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug development for the treatment of a number of pathological states. A novel peptide producing a significant potentiating effect on allyl isothiocy...

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Published in:	The Journal of biological chemistry Vol. 292; no. 7; pp. 2992 - 3004
Main Authors:	Logashina, Yulia A., Mosharova, Irina V., Korolkova, Yulia V., Shelukhina, Irina V., Dyachenko, Igor A., Palikov, Victor A., Palikova, Yulia A., Murashev, Arkadii N., Kozlov, Sergey A., Stensvåg, Klara, Andreev, Yaroslav A.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 17-02-2017 American Society for Biochemistry and Molecular Biology
Subjects:	Amino Acid Sequence Analgesics - pharmacology Animals Base Sequence Chemistry: 440 CHO Cells Cricetulus inflammation Kjemi: 440 marine bioprospecting Matematikk og Naturvitenskap: 400 Mathematics and natural science: 400 Mice neuron Organic chemistry: 441 Organisk kjemi: 441 pain peptides Peptides - chemistry Peptides - isolation & purification Peptides - pharmacology potentiating effect Protein Structure and Folding receptor sea anemones Sea Anemones - chemistry Sequence Homology, Amino Acid Transient Receptor Potential Channels - drug effects TRPA1 VDP marine bioprospecting potentiating effect pain receptor TRPA1 inflammation sea anemones neuron peptides
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Abstract	The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug development for the treatment of a number of pathological states. A novel peptide producing a significant potentiating effect on allyl isothiocyanate- and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone Metridium senile. It is a 35-amino acid peptide cross-linked by two disulfide bridges named τ-AnmTX Ms 9a-1 (short name Ms 9a-1) according to a structure similar to other sea anemone peptides belonging to structural group 9a. The structures of the two genes encoding the different precursor proteins of Ms 9a-1 were determined. Peptide Ms 9a-1 acted as a positive modulator of TRPA1 in vitro but did not cause pain or thermal hyperalgesia when injected into the hind paw of mice. Intravenous injection of Ms 9a-1 (0.3 mg/kg) produced a significant decrease in the nociceptive and inflammatory response to allyl isothiocyanate (the agonist of TRPA1) and reversed CFA (Complete Freund's Adjuvant)-induced inflammation and thermal hyperalgesia. Taken together these data support the hypothesis that Ms 9a-1 potentiates the response of TRPA1 to endogenous agonists followed by persistent functional loss of TRPA1-expressing neurons. We can conclude that TRPA1 potentiating may be useful as a therapeutic approach as Ms 9a-1 produces significant analgesic and anti-inflammatory effects in mice models of pain.
AbstractList	The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug development for the treatment of a number of pathological states. A novel peptide producing a significant potentiating effect on allyl isothiocyanate- and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone It is a 35-amino acid peptide cross-linked by two disulfide bridges named τ-AnmTX Ms 9a-1 (short name Ms 9a-1) according to a structure similar to other sea anemone peptides belonging to structural group 9a. The structures of the two genes encoding the different precursor proteins of Ms 9a-1 were determined. Peptide Ms 9a-1 acted as a positive modulator of TRPA1 but did not cause pain or thermal hyperalgesia when injected into the hind paw of mice. Intravenous injection of Ms 9a-1 (0.3 mg/kg) produced a significant decrease in the nociceptive and inflammatory response to allyl isothiocyanate (the agonist of TRPA1) and reversed CFA (Complete Freund's Adjuvant)-induced inflammation and thermal hyperalgesia. Taken together these data support the hypothesis that Ms 9a-1 potentiates the response of TRPA1 to endogenous agonists followed by persistent functional loss of TRPA1-expressing neurons. We can conclude that TRPA1 potentiating may be useful as a therapeutic approach as Ms 9a-1 produces significant analgesic and anti-inflammatory effects in mice models of pain. The Transient Receptor Potential Ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drugs development for treatment of a number of pathological states. A novel peptide producing significant potentiating effect (up to ~90%) on AITC- and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone Metridium senile. It is 35 amino acid peptide cross-linked by two disulfide bridges, named τ-AnmTX Ms 9a-1 (short name Ms 9a-1) according to structure similarity to other sea anemone peptides belonging to structural group 9a. The structure of two genes encoding different precursor proteins of Ms 9a-1 were determined. Peptide Ms 9a-1 acted as a positive modulator of TRPA1 in vitro but did not cause pain or thermal hyperalgesia when injected in mice hind paw. Intravenous injection of Ms 9a-1 (0.3 mg/kg) produced significant decrease of nociceptive and inflammatory response to AITC (agonist of TRPA1) and reversed CFA-induced inflammation and thermal hyperalgesia. Taken together, these data support the hypothesis that Ms 9a-1 potentiates response of TRPA1 to endogenous agonists followed by persistent functional loss of TRPA1-expressing neurons. We can conclude that TRPA1 potentiating may be useful as therapeutic approach since Ms 9a-1 produce significant analgesic and anti- inflammatory effect in mice models of pain. The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug development for the treatment of a number of pathological states. A novel peptide producing a significant potentiating effect on allyl isothiocyanate- and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone Metridium senile. It is a 35-amino acid peptide cross-linked by two disulfide bridges named τ-AnmTX Ms 9a-1 (short name Ms 9a-1) according to a structure similar to other sea anemone peptides belonging to structural group 9a. The structures of the two genes encoding the different precursor proteins of Ms 9a-1 were determined. Peptide Ms 9a-1 acted as a positive modulator of TRPA1 in vitro but did not cause pain or thermal hyperalgesia when injected into the hind paw of mice. Intravenous injection of Ms 9a-1 (0.3 mg/kg) produced a significant decrease in the nociceptive and inflammatory response to allyl isothiocyanate (the agonist of TRPA1) and reversed CFA (Complete Freund's Adjuvant)-induced inflammation and thermal hyperalgesia. Taken together these data support the hypothesis that Ms 9a-1 potentiates the response of TRPA1 to endogenous agonists followed by persistent functional loss of TRPA1-expressing neurons. We can conclude that TRPA1 potentiating may be useful as a therapeutic approach as Ms 9a-1 produces significant analgesic and anti-inflammatory effects in mice models of pain. The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug development for the treatment of a number of pathological states. A novel peptide producing a significant potentiating effect on allyl isothiocyanate- and diclofenac-induced currents of TRPA1 was isolated from the venom of sea anemone Metridium senile. It is a 35-amino acid peptide cross-linked by two disulfide bridges named τ-AnmTX Ms 9a-1 (short name Ms 9a-1) according to a structure similar to other sea anemone peptides belonging to structural group 9a. The structures of the two genes encoding the different precursor proteins of Ms 9a-1 were determined. Peptide Ms 9a-1 acted as a positive modulator of TRPA1 in vitro but did not cause pain or thermal hyperalgesia when injected into the hind paw of mice. Intravenous injection of Ms 9a-1 (0.3 mg/kg) produced a significant decrease in the nociceptive and inflammatory response to allyl isothiocyanate (the agonist of TRPA1) and reversed CFA (Complete Freund's Adjuvant)-induced inflammation and thermal hyperalgesia. Taken together these data support the hypothesis that Ms 9a-1 potentiates the response of TRPA1 to endogenous agonists followed by persistent functional loss of TRPA1-expressing neurons. We can conclude that TRPA1 potentiating may be useful as a therapeutic approach as Ms 9a-1 produces significant analgesic and anti-inflammatory effects in mice models of pain.
Author	Dyachenko, Igor A. Palikova, Yulia A. Korolkova, Yulia V. Shelukhina, Irina V. Logashina, Yulia A. Murashev, Arkadii N. Mosharova, Irina V. Kozlov, Sergey A. Palikov, Victor A. Stensvåg, Klara Andreev, Yaroslav A.
Author_xml	– sequence: 1 givenname: Yulia A. surname: Logashina fullname: Logashina, Yulia A. organization: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia – sequence: 2 givenname: Irina V. surname: Mosharova fullname: Mosharova, Irina V. organization: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia – sequence: 3 givenname: Yulia V. surname: Korolkova fullname: Korolkova, Yulia V. organization: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia – sequence: 4 givenname: Irina V. surname: Shelukhina fullname: Shelukhina, Irina V. organization: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia – sequence: 5 givenname: Igor A. surname: Dyachenko fullname: Dyachenko, Igor A. organization: Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow, Russia – sequence: 6 givenname: Victor A. surname: Palikov fullname: Palikov, Victor A. organization: Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow, Russia – sequence: 7 givenname: Yulia A. surname: Palikova fullname: Palikova, Yulia A. organization: Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow, Russia – sequence: 8 givenname: Arkadii N. surname: Murashev fullname: Murashev, Arkadii N. organization: Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290 Pushchino, Moscow, Russia – sequence: 9 givenname: Sergey A. surname: Kozlov fullname: Kozlov, Sergey A. organization: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia – sequence: 10 givenname: Klara surname: Stensvåg fullname: Stensvåg, Klara organization: Norwegian College of Fishery Science, University of Tromsø, N9037 Tromsø, Norway – sequence: 11 givenname: Yaroslav A. surname: Andreev fullname: Andreev, Yaroslav A. email: ay@land.ru organization: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10,117997 Moscow, Russia
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Copyright	2017 © 2017 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. 2017 by The American Society for Biochemistry and Molecular Biology, Inc. info:eu-repo/semantics/openAccess 2017 by The American Society for Biochemistry and Molecular Biology, Inc. 2017 The American Society for Biochemistry and Molecular Biology, Inc.
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Keywords	marine bioprospecting potentiating effect pain receptor TRPA1 inflammation sea anemones neuron peptides
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Snippet	The transient receptor potential ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drug... The Transient Receptor Potential Ankyrin-repeat 1 (TRPA1) is an important player in pain and inflammatory pathways. It is a promising target for novel drugs...
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SubjectTerms	Amino Acid Sequence Analgesics - pharmacology Animals Base Sequence Chemistry: 440 CHO Cells Cricetulus inflammation Kjemi: 440 marine bioprospecting Matematikk og Naturvitenskap: 400 Mathematics and natural science: 400 Mice neuron Organic chemistry: 441 Organisk kjemi: 441 pain peptides Peptides - chemistry Peptides - isolation & purification Peptides - pharmacology potentiating effect Protein Structure and Folding receptor sea anemones Sea Anemones - chemistry Sequence Homology, Amino Acid Transient Receptor Potential Channels - drug effects TRPA1 VDP
Title	Peptide from Sea Anemone Metridium senile Affects Transient Receptor Potential Ankyrin-repeat 1 (TRPA1) Function and Produces Analgesic Effect
URI	https://dx.doi.org/10.1074/jbc.M116.757369 https://www.ncbi.nlm.nih.gov/pubmed/28077580 https://search.proquest.com/docview/1858106278 http://hdl.handle.net/10037/13816 https://pubmed.ncbi.nlm.nih.gov/PMC5314193
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