title: Sodium antimony gluconate induces generation of reactive oxygen species and nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase activation in Leishmania donovani-infected macrophages.
creator: Mookerjee Basu, Jayati
creator: Mookerjee, Ananda
creator: Sen, Prosenjit
creator: Bhaumik, Suniti
creator: Sen, Pradip
creator: Banerjee, Subha
creator: Naskar, Ksudiram
creator: Choudhuri, Soumitra K
creator: Saha, B
creator: Raha, Sanghamitra
creator: Roy, Syamal
subject: QD Chemistry
description: Pentavalent antimony complexes, such as sodium stibogluconate and sodium antimony gluconate (SAG), are still the first choice for chemotherapy against various forms of leishmaniasis, including visceral leishmaniasis, or kala-azar. Although the requirement of a somewhat functional immune system for the antileishmanial action of antimony was reported previously, the cellular and molecular mechanism of action of SAG was not clear. Herein, we show that SAG induces extracellular signal-regulated kinase 1 (ERK-1) and ERK-2 phosphorylation through phosphoinositide 3-kinase (PI3K), protein kinase C, and Ras activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation through PI3K and Akt activation. ERK-1 and ERK-2 activation results in an increase in the production of reactive oxygen species (ROS) 3 to 6 h after SAG treatment, while p38 MAPK activation and subsequent tumor necrosis factor alpha release result in the production of nitric oxide (NO) 24 h after SAG treatment. Thus, this study has provided the first evidence that SAG treatment induces activation of some important components of the intracellular signaling pathway, which results in an early wave of ROS-dependent parasite killing and a stronger late wave of NO-dependent parasite killing. This opens up the possibility of this metalloid chelate being used in the treatment of various diseases either alone or in combination with other drugs and vaccines.
publisher: ASM
date: 2006-05
type: Article
type: PeerReviewed
format: application/pdf
identifier: http://crdd.osdd.net/open/1031/1/sen2006.3.pdf
relation: http://aac.asm.org/content/50/5/1788.long
identifier:   Mookerjee Basu, Jayati and Mookerjee, Ananda and Sen, Prosenjit and Bhaumik, Suniti and Sen, Pradip and Banerjee, Subha and Naskar, Ksudiram and Choudhuri, Soumitra K and Saha, B and Raha, Sanghamitra and Roy, Syamal  (2006) Sodium antimony gluconate induces generation of reactive oxygen species and nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase activation in Leishmania donovani-infected macrophages.  Antimicrobial agents and chemotherapy, 50 (5).  pp. 1788-97.  ISSN 0066-4804     
relation: http://crdd.osdd.net/open/1031/