Vaš brskalnik ne omogoča JavaScript!
JavaScript je nujen za pravilno delovanje teh spletnih strani. Omogočite JavaScript ali pa uporabite sodobnejši brskalnik.
Nacionalni portal odprte znanosti
Odprta znanost
DiKUL
slv
|
eng
Iskanje
Brskanje
Novo v RUL
Kaj je RUL
V številkah
Pomoč
Prijava
A putative serine protease is required to initiate the RIPK3-MLKL—mediated necroptotic death pathway in neutrophils
ID
Wang, Xiaoliang
(
Avtor
),
ID
Avsec, Damjan
(
Avtor
),
ID
Obreza, Aleš
(
Avtor
),
ID
Yousefi, Shida
(
Avtor
),
ID
Mlinarič-Raščan, Irena
(
Avtor
),
ID
Simon, Hans-Uwe
(
Avtor
)
PDF - Predstavitvena datoteka,
prenos
(1,47 MB)
MD5: E5CFE3A3FEAC2B4CEAB90A20381A4A6D
URL - Izvorni URL, za dostop obiščite
https://www.frontiersin.org/articles/10.3389/fphar.2020.614928/full
Galerija slik
Izvleček
Adhesion receptors, such as CD44, have been shown to activate receptor interacting protein kinase-3 (RIPK3)—mixed lineage kinase-like (MLKL) signaling, leading to a non-apoptotic cell death in human granulocyte/macrophage colony-stimulating factor (GM-CSF) – primed neutrophils. The signaling events of this necroptotic pathway, however, remain to be investigated. In the present study, we report the design, synthesis, and characterization of a series of novel serine protease inhibitors. Two of these inhibitors, compounds 1 and 3, were able to block CD44-triggered necroptosis in GM-CSF-primed neutrophils. Both inhibitors prevented the activation of MLKL, p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3’—kinase (PI3K), hence blocking the increased levels of reactive oxygen species (ROS) required for cell death. Although compounds one and three partially inhibited isolated human neutrophil elastase (HNE) activity, we obtained no pharmacological evidence that HNE is involved in the initiation of this death pathway within a cellular context. Interestingly, neither serine protease inhibitor had any effect on FAS receptor-mediated apoptosis. Taken together, these results suggest that a serine protease is involved in non-apoptotic CD44-triggered RIPK3-MLKL-dependent neutrophil cell death, but not FAS receptor-mediated caspase-dependent apoptosis. Thus, a pharmacological block on serine proteases might be beneficial for preventing exacerbation of disease in neutrophilic inflammatory responses.
Jezik:
Angleški jezik
Ključne besede:
necroptosis
,
neutrophil
,
serine protease
,
signal transduction
,
small molecule inhibitor
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
FFA - Fakulteta za farmacijo
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2021
Št. strani:
10 str.
Številčenje:
Vol. 11, art. 614928
PID:
20.500.12556/RUL-141388
UDK:
576.36
ISSN pri članku:
1663-9812
DOI:
10.3389/fphar.2020.614928
COBISS.SI-ID:
48117763
Datum objave v RUL:
29.09.2022
Število ogledov:
1645
Število prenosov:
65
Metapodatki:
Citiraj gradivo
Navadno besedilo
BibTeX
EndNote XML
EndNote/Refer
RIS
ABNT
ACM Ref
AMA
APA
Chicago 17th Author-Date
Harvard
IEEE
ISO 690
MLA
Vancouver
:
Kopiraj citat
Objavi na:
Gradivo je del revije
Naslov:
Frontiers in pharmacology
Skrajšan naslov:
Front Pharmacol
Založnik:
Frontiers Media
ISSN:
1663-9812
COBISS.SI-ID:
29551833
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
nekroptoza
,
serinske proteaze
,
zaviralci molekul
,
receptor CD44
,
apoptoza
Projekti
Financer:
SNSF - Swiss National Science Foundation
Program financ.:
Project funding
Številka projekta:
31003A_173215
Naslov:
Molecular mechanisms of neutrophil extracellular trap (NET) formation
Financer:
SNSF - Swiss National Science Foundation
Program financ.:
Project funding
Številka projekta:
310030_184816
Naslov:
Molecular pathways regulating eosinophil numbers and functions
Financer:
EC - European Commission
Program financ.:
H2020
Številka projekta:
642295
Naslov:
Exploiting MELanoma disease comPLEXity to address European research training needs in translational cancer systems biology and cancer systems medicine
Akronim:
MEL-PLEX
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P1-0208
Naslov:
Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin
Podobna dela
Podobna dela v RUL:
Podobna dela v drugih slovenskih zbirkah:
Nazaj