Inhibition of NOS-2 induction in LPS-stimulated J774.2 cells by 1,5-isoquinolinediol, an inhibitor of PARP

• Autorzy: Olszanecki R. , Gebska A. , Jawien J. , Jakubowski A. , Korbut R.
• Języki publikacji: EN

Abstrakty

EN

Activation of both poly (ADP-ribose) polymerase (PARP) and inducible nitric oxide synthase (NOS-2) have been implicated in the pathogenesis of various forms of inflammation, therefore compounds which may simultaneously inhibit both pathways are of potential therapeutic interest. We tested the influence of potent inhibitor of PARP, 1, 5-isoquinolinediol (ISO), on NOS-2 induction in model of mouse macrophages (cell line J774.2) stimulated with lipopolysaccharide (1 µg/ml). Pretreatment with ISO (1-300 µM) resulted in dose-dependent inhibition of accumulation of NOS-2-derived nitrite in culture medium (IC50 = 9,3 µM) as well as inhibition of NOS-2 protein induction in cultured J774.2 cells; ISO given 10 hours after LPS did not influence activity of NOS-2. Interestingly, another PARP inhibitor, 3-aminobenzamide (3-AB, 10-3000 µM), did not influence 24-hr nitrite accumulation in J774.2 cell culture, either administered 15 minutes prior to LPS or 10 hrs after LPS. Scavenging of reactive oxygen species by use of mixture of SOD and catalase (SOD/Cat, 100/300 - 1000/3000 U/ml) as well as cell permeable SOD-mimetic [Mn(III)TBAP, 1- 100 µM], did not influence NOS-2 induction in J774.2 cells. In summary, we identified 1, 5-isoquinoline as potent inhibitor of induction of NOS-2 in LPS-treated mouse macrophages. The exact mechanism of inhibitory action of this compound on NOS-2 induction requires further investigation.

Słowa kluczowe

EN

1,5-isoquinolinediol; pathogenesis; nitric oxide synthase; lipopolysaccharide; macrophage; inflammation; inhibition

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2006
• Tom: 57
• Numer: 1
• Opis fizyczny: p.109-117,fig.,ref.

Twórcy

autor

Olszanecki R.

• Jagiellonian University School of Medicine, 16 Grzegorzecka str., 31-531 Krakow, Poland

autor

Gebska A.

autor

Jawien J.

autor

Jakubowski A.

autor

Korbut R.