A novel Kunitz protein with proposed dual function from
Eudiplozoon nipponicum (Monogenea) impairs haemostasis and
action of complement in vitro

J 2019

A novel Kunitz protein with proposed dual function from Eudiplozoon nipponicum (Monogenea) impairs haemostasis and action of complement in vitro

JEDLIČKOVÁ, Lucie, Jan DVOŘÁK, Ingrid HRACHOVINOVÁ, Lenka ULRYCHOVÁ, Martin KAŠNÝ et. al.

Základní údaje

Originální název

A novel Kunitz protein with proposed dual function from Eudiplozoon nipponicum (Monogenea) impairs haemostasis and action of complement in vitro

Autoři

JEDLIČKOVÁ, Lucie (203 Česká republika), Jan DVOŘÁK (203 Česká republika), Ingrid HRACHOVINOVÁ (203 Česká republika), Lenka ULRYCHOVÁ (203 Česká republika), Martin KAŠNÝ (203 Česká republika, garant, domácí) a Libor MIKEŠ (203 Česká republika)

Vydání

International Journal for Parasitology, Oxford, Elsevier Science Ltd. 2019, 0020-7519

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10613 Zoology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.530

Kód RIV

RIV/00216224:14310/19:00108143

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.ijpara.2018.11.010

UT WoS

000466453400002

Klíčová slova anglicky

Anticoagulant; Kunitz; Peptidase inhibitor; Factor X; Plasmin; Haematophagy; Helminth; Diplozoidae

Štítky

CF PROT, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 3. 2020 17:54, Mgr. Marie Šípková, DiS.

Anotace

V originále

Serine peptidases are involved in many physiological processes including digestion, haemostasis and complement cascade. Parasites regulate activities of host serine peptidases to their own benefit, employing various inhibitors, many of which belong to the Kunitz-type protein family. In this study, we confirmed the presence of potential anticoagulants in protein extracts of the haematophagous monogenean Eudiplozoon nipponicum which parasitizes the common carp. We then focused on a Kunitz protein (EnKT1) discovered in the E. nipponicum transcriptome, which structurally resembles textilinin-1, an antihemorrhagic snake venom factor from Pseudonaja textilis. The protein was recombinantly expressed, purified and biochemically characterised. The recombinant EnKT1 did inhibit in vitro activity of Factor Xa of the coagulation cascade, but exhibited a higher activity against plasmin and plasma kallikrein, which participate in fibrinolysis, production of kinins, and complement activation. Anti-coagulation properties of EnKT1 based on the inhibition of Factor Xa were confirmed by thromboe-lastography, but no effect on fibrinolysis was observed. Moreover, we discovered that EnKT1 significantly impairs the function of fish complement, possibly by inhibiting plasmin or Factor Xa which can act as a C3 and C5 convertase. We localised Enkt1 transcripts and protein within haematin digestive cells of the parasite by RNA in situ hybridisation and immunohistochemistry, respectively. Based on these results, we suggest that the secretory Kunitz protein of E. nipponicum has a dual function. In particular, it impairs both haemostasis and complement activation in vitro, and thus might facilitate digestion of a host's blood and protect a parasite's gastrodermis from damage by the complement. This study presents, to our knowledge, the first characterisation of a Kunitz protein from monogeneans and the first example of a parasite Kunitz inhibitor that impairs the function of the complement. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of Australian Society for Parasitology.

Návaznosti

GAP506/12/1258, projekt VaV

Název: Interakce hostitel-parazit u krevsajících diplozoidních monogeneí: Výzkum vysoce specializovaných adaptací k parazitismu

Investor: Grantová agentura ČR, Interakce hostitel-parazit u krevsajících diplozoidních monogeneí: Výzkum vysoce specializovaných adaptací k parazitismu

GBP505/12/G112, projekt VaV

Název: ECIP - Evropské centrum ichtyoparazitologie

Investor: Grantová agentura ČR, ECIP - Evropské centrum ichtyoparazitologie

LM2015043, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

Citovat

JEDLIČKOVÁ, Lucie, Jan DVOŘÁK, Ingrid HRACHOVINOVÁ, Lenka ULRYCHOVÁ, Martin KAŠNÝ a Libor MIKEŠ. A novel Kunitz protein with proposed dual function from Eudiplozoon nipponicum (Monogenea) impairs haemostasis and action of complement in vitro. International Journal for Parasitology. Oxford: Elsevier Science Ltd., 2019, roč. 49, č. 5, s. 337-346. ISSN 0020-7519. Dostupné z: https://dx.doi.org/10.1016/j.ijpara.2018.11.010.

@article{1617117,
   author = {Jedličková, Lucie and Dvořák, Jan and Hrachovinová, Ingrid and Ulrychová, Lenka and Kašný, Martin and Mikeš, Libor},
   article_location = {Oxford},
   article_number = {5},
   doi = {http://dx.doi.org/10.1016/j.ijpara.2018.11.010},
   keywords = {Anticoagulant; Kunitz; Peptidase inhibitor; Factor X; Plasmin; Haematophagy; Helminth; Diplozoidae},
   language = {eng},
   issn = {0020-7519},
   journal = {International Journal for Parasitology},
   title = {A novel Kunitz protein with proposed dual function from Eudiplozoon nipponicum (Monogenea) impairs haemostasis and action of complement in vitro},
   url = {https://www.sciencedirect.com/science/article/pii/S0020751919300268?via%3Dihub},
   volume = {49},
   year = {2019}
}

TY  - JOUR
ID  - 1617117
AU  - Jedličková, Lucie - Dvořák, Jan - Hrachovinová, Ingrid - Ulrychová, Lenka - Kašný, Martin - Mikeš, Libor
PY  - 2019
TI  - A novel Kunitz protein with proposed dual function from Eudiplozoon nipponicum (Monogenea) impairs haemostasis and action of complement in vitro
JF  - International Journal for Parasitology
VL  - 49
IS  - 5
SP  - 337-346
EP  - 337-346
PB  - Elsevier Science Ltd.
SN  - 00207519
KW  - Anticoagulant
KW  - Kunitz
KW  - Peptidase inhibitor
KW  - Factor X
KW  - Plasmin
KW  - Haematophagy
KW  - Helminth
KW  - Diplozoidae
UR  - https://www.sciencedirect.com/science/article/pii/S0020751919300268?via%3Dihub
L2  - https://www.sciencedirect.com/science/article/pii/S0020751919300268?via%3Dihub
N2  - Serine peptidases are involved in many physiological processes including digestion, haemostasis and complement cascade. Parasites regulate activities of host serine peptidases to their own benefit, employing various inhibitors, many of which belong to the Kunitz-type protein family. In this study, we confirmed the presence of potential anticoagulants in protein extracts of the haematophagous monogenean Eudiplozoon nipponicum which parasitizes the common carp. We then focused on a Kunitz protein (EnKT1) discovered in the E. nipponicum transcriptome, which structurally resembles textilinin-1, an antihemorrhagic snake venom factor from Pseudonaja textilis. The protein was recombinantly expressed, purified and biochemically characterised. The recombinant EnKT1 did inhibit in vitro activity of Factor Xa of the coagulation cascade, but exhibited a higher activity against plasmin and plasma kallikrein, which participate in fibrinolysis, production of kinins, and complement activation. Anti-coagulation properties of EnKT1 based on the inhibition of Factor Xa were confirmed by thromboe-lastography, but no effect on fibrinolysis was observed. Moreover, we discovered that EnKT1 significantly impairs the function of fish complement, possibly by inhibiting plasmin or Factor Xa which can act as a C3 and C5 convertase. We localised Enkt1 transcripts and protein within haematin digestive cells of the parasite by RNA in situ hybridisation and immunohistochemistry, respectively. Based on these results, we suggest that the secretory Kunitz protein of E. nipponicum has a dual function. In particular, it impairs both haemostasis and complement activation in vitro, and thus might facilitate digestion of a host's blood and protect a parasite's gastrodermis from damage by the complement. This study presents, to our knowledge, the first characterisation of a Kunitz protein from monogeneans and the first example of a parasite Kunitz inhibitor that impairs the function of the complement. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of Australian Society for Parasitology.
ER  -

JEDLIČKOVÁ, Lucie, Jan DVOŘÁK, Ingrid HRACHOVINOVÁ, Lenka ULRYCHOVÁ, Martin KAŠNÝ a Libor MIKEŠ. A novel Kunitz protein with proposed dual function from Eudiplozoon nipponicum (Monogenea) impairs haemostasis and action of complement in vitro. \textit{International Journal for Parasitology}. Oxford: Elsevier Science Ltd., 2019, roč.~49, č.~5, s.~337-346. ISSN~0020-7519. Dostupné z: https://dx.doi.org/10.1016/j.ijpara.2018.11.010.

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