Cross-talk between nitric oxide and transforming growth factor β in malaria

Yoram Vodovotz, Ruben Zamora, Matthew J. Lieber, Shirley Luckhart

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Malaria has re-emerged as a global health problem, leading to an increased focus on the cellular and molecular biology of the mosquito Anopheles and the parasite Plasmodium with the goal of identifying novel points of intervention in the parasite life cycle. Anti-parasite defenses mounted by both mammalian hosts and Anopheles can suppress the growth of Plasmodium. Nonetheless, the parasite is able to escape complete elimination in vivo, perhaps by thwarting or co-opting these mechanisms for its own survival, as do numerous other pathogens. Among the defense systems used by the mammalian host against Plasmodium is the synthesis of nitric oxide (NO), catalyzed by an inducible NO synthase (iNOS). Nitric oxide produced by the action of an inducible Anopheles stephensi NO synthase (AsNOS) may be central to the anti-parasitic arsenal of this mosquito. In mammals, iNOS can be modulated by members of the transforming growth factor-β (TGF-β) cytokine superfamily. Transforming growth factor-β is produced as an inactive precursor that is activated following dissociation of certain inhibitory proteins, a process that can be promoted by reaction products of NO as well as by hemin. Ingestion by Anopheles of blood containing Plasmodium initiates parasite development, blood digestion which results in the accumulation of hematin (hemin) in the insect midgut, and induction of both AsNOS and TGF-β-like (As60A) gene expression in the midgut epithelium. Active mammalian TGF-β1 can be detected in the A. stephensi midgut up to 48h postingestion and latent TGF-β1 can be activated by midgut components in vitro, a process that is potentiated by NO and that may involve hematin. Further, mammalian TGF-β1 is perceived as a cytokine by A. stephensi cells in vitro and can alter Plasmodium development in vivo. Bloodfeeding by Anopheles, therefore, results in a juxtaposition of evolutionarily conserved mosquito and mammalian TGF-β superfamily homologs that may influence transmission dynamics of Plasmodium in endemic regions.

Original languageEnglish (US)
Pages (from-to)787-797
Number of pages11
JournalCurrent Molecular Medicine
Volume4
Issue number7
DOIs
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Transforming Growth Factors
Anopheles
Plasmodium
Malaria
Nitric Oxide
Parasites
Hemin
Culicidae
Nitric Oxide Synthase
Blood
Cytology
Cytokines
Arsenals
Molecular biology
Mammals
Nitric Oxide Synthase Type II
Pathogens
Medical problems
Life Cycle Stages
Reaction products

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cross-talk between nitric oxide and transforming growth factor β in malaria. / Vodovotz, Yoram; Zamora, Ruben; Lieber, Matthew J.; Luckhart, Shirley.

In: Current Molecular Medicine, Vol. 4, No. 7, 11.2004, p. 787-797.

Research output: Contribution to journalArticle

Vodovotz, Yoram ; Zamora, Ruben ; Lieber, Matthew J. ; Luckhart, Shirley. / Cross-talk between nitric oxide and transforming growth factor β in malaria. In: Current Molecular Medicine. 2004 ; Vol. 4, No. 7. pp. 787-797.
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