a(1)-Adrenoceptor agonist methoxamine inhibits base excision
repair via inhibition of apurinic/apyrimidinic endonuclease 1
(APE1)

J 2023

a(1)-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1)

KOHUTOVÁ, Aneta; Dita MÜNZOVÁ; Martin PEŠL a Vladimír ROTREKL

Základní údaje

Originální název

a(1)-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1)

Autoři

KOHUTOVÁ, Aneta; Dita MÜNZOVÁ; Martin PEŠL a Vladimír ROTREKL

Vydání

Acta Pharmaceutica, WARSAW, SCIENDO, 2023, 1330-0075

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Polsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.100

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/23:00131202

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

methoxamine; base excision repair; apurinic; apyrimidinic endonuclease APE1; alpha 1-adrenoceptor agonist

Štítky

14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 11. 7. 2023 09:53, Mgr. Tereza Miškechová

Anotace

V originále

Methoxamine (Mox) is a well-known a1-adrenoceptor agonist, clinically used as a longer-acting analogue of epinephrine. 1R,2S-Mox (NRL001) has been also undergoing clinical testing to increase the canal resting pressure in patients with bowel incontinence. Here we show, that Mox hydrochloride acts as an inhibitor of base excision repair (BER). The effect is mediated by the inhibition of apurinic/apyrimidinic endonuclease APE1. We link this observation to our previous report showing the biologically relevant effect of Mox on BER - prevention of converting oxidative DNA base damage to double-stranded breaks. We demonstrate that its effect is weaker, but still significant when compared to a known BER inhibitor methoxyamine (MX). We further determined Mox's relative IC50 at 19 mmol L-1, demonstrating a significant effect of Mox on APE1 activity in clinically relevant concentrations.

Návaznosti

LX22NPO5104, projekt VaV

Název: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění (Akronym: CarDia)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní institut pro léčbu metabolických a kardiovaskulárních onemocnění, 5.1 EXCELES

Přiložené soubory

a_1_-Adrenoceptor_agonist_methoxamine_inhibits_base_excision_repair_via_inhibition_of_apurinic_apyrimidinic_endonuclease_1__APE1_.pdf

Citovat

KOHUTOVÁ, Aneta; Dita MÜNZOVÁ; Martin PEŠL a Vladimír ROTREKL. a(1)-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1). Acta Pharmaceutica. WARSAW: SCIENDO, 2023, roč. 73, č. 2, s. 281-291. ISSN 1330-0075. Dostupné z: https://doi.org/10.2478/acph-2023-0012.

@article{2296994,
   author = {Kohutová, Aneta and Münzová, Dita and Pešl, Martin and Rotrekl, Vladimír},
   article_location = {WARSAW},
   article_number = {2},
   doi = {https://doi.org/10.2478/acph-2023-0012},
   keywords = {methoxamine; base excision repair; apurinic; apyrimidinic endonuclease APE1; alpha 1-adrenoceptor agonist},
   language = {eng},
   issn = {1330-0075},
   journal = {Acta Pharmaceutica},
   title = {a(1)-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1)},
   url = {https://sciendo.com/article/10.2478/acph-2023-0012},
   volume = {73},
   year = {2023}
}

TY  - JOUR
ID  - 2296994
AU  - Kohutová, Aneta - Münzová, Dita - Pešl, Martin - Rotrekl, Vladimír
PY  - 2023
TI  - a(1)-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1)
JF  - Acta Pharmaceutica
VL  - 73
IS  - 2
SP  - 281-291
EP  - 281-291
PB  - SCIENDO
SN  - 13300075
KW  - methoxamine
KW  - base excision repair
KW  - apurinic
KW  - apyrimidinic endonuclease APE1
KW  - alpha 1-adrenoceptor agonist
UR  - https://sciendo.com/article/10.2478/acph-2023-0012
N2  - Methoxamine (Mox) is a well-known a1-adrenoceptor agonist, clinically used as a longer-acting analogue of epinephrine. 1R,2S-Mox (NRL001) has been also undergoing clinical testing to increase the canal resting pressure in patients with bowel incontinence. Here we show, that Mox hydrochloride acts as an inhibitor of base excision repair (BER). The effect is mediated by the inhibition of apurinic/apyrimidinic endonuclease APE1. We link this observation to our previous report showing the biologically relevant effect of Mox on BER - prevention of converting oxidative DNA base damage to double-stranded breaks. We demonstrate that its effect is weaker, but still significant when compared to a known BER inhibitor methoxyamine (MX). We further determined Mox's relative IC50 at 19 mmol L-1, demonstrating a significant effect of Mox on APE1 activity in clinically relevant concentrations.
ER  -

KOHUTOVÁ, Aneta; Dita MÜNZOVÁ; Martin PEŠL a Vladimír ROTREKL. a(1)-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1). \textit{Acta Pharmaceutica}. WARSAW: SCIENDO, 2023, roč.~73, č.~2, s.~281-291. ISSN~1330-0075. Dostupné z: https://doi.org/10.2478/acph-2023-0012.

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