Monika C. Žužek (Avtor), Adrijan Ivanušec (Avtor), Julija Herman (Avtor), Jernej Šribar (Avtor), Adrijana Leonardi (Avtor), Robert Frangež (Avtor), Igor Križaj (Avtor)

Povzetek

Presynaptic- or β-neurotoxicity of secreted phospholipases A2 (sPLA2) is a complex process. For full expression of β-neurotoxicity, the enzymatic activity of the toxin is essential. However, it has been shown that not all toxic effects of a β-neurotoxin depend on its enzymatic activity, for example, the inhibition of mitochondrial cytochrome c oxidase. The main objective of this study was to verify whether it is possible to observe and study the phospholipase-independent actions of β-neurotoxins by a standard ex vivo twitch-tension experimental approach. To this end, we compared the effects of a potent snake venom β-neurotoxin, ammodytoxin A (AtxA), and its enzymatically inactive mutant AtxA(D49S) on muscle contraction of the mouse phrenic nerve-hemidiaphragm preparation. While AtxA significantly affected the amplitude of the indirectly evoked isometric muscle contraction, the resting tension of the neuromuscular (NM) preparation, the amplitude of the end-plate potential (EPP), the EPP half decay time and the resting membrane potential, AtxA(D49S) without enzymatic activity did not. From this, we can conclude that the effects of AtxA independent of enzymatic activity cannot be studied with classical electrophysiological measurements on the isolated NM preparation. Our results also suggest that the inhibition of cytochrome c oxidase activity by AtxA is not involved in the rapid NM blockade by this β-neurotoxin, but that its pathological consequences are rather long-term. Interestingly, in our experimental setup, AtxA upon direct stimulation reduced the amplitude of muscle contraction and induced contracture of the hemidiaphragm, effects that could be interpreted as myotoxic.

Ključne besede

kačji strup;encimska aktivnost;snake venom;ammodytoxin;secreted phospholipase A2;anzymatic activity;cytochrome c oxidase;ß-neurotoxicity;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: IJS - Institut Jožef Stefan
UDK: 615:616-092:636.09
COBISS: 200247555 Povezava se bo odprla v novem oknu
ISSN: 1879-3150
Št. ogledov: 65
Št. prenosov: 10
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: Snakes;Strupene kače;Encimska aktivnost;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-6
Zvezek: ǂVol. ǂ247, [article no.] 107833
Čas izdaje: 2024
DOI: 10.1016/j.toxicon.2024.107833
ID: 24512124