Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Products of the kynurenine pathway of tryptophan metabolism have been implicated in the pathogenesis of murine and human cerebral malaria. Indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme in this pathway and we have developed an immunohistochemical method for its detection in tissues from normal and malaria-infected mice. Mice were infected with Plasmodium berghei ANKA, a murine model of cerebral malaria, or P. berghei K173, a non-cerebral malaria model. Vascular endothelial cells were the primary sites of indoleamine 2,3-dioxygenase expression in both types of malaria infection and this response was systemic, with positive staining of vascular endothelium in all tissues examined. No indoleamine 2,3-dioxygenase expression was detected in uninfected or interferon-gamma-/- mice. Corroborative data were obtained using quantitative reverse transcription PCR for indoleamine 2,3-dioxygenase mRNA. These results suggest that interferon-gamma-dependent indoleamine 2,3-dioxygenase expression is part of a normal systemic host response to the parasite, perhaps performing some tissue protective functions that may become deranged under some circumstances and contribute to the pathogenesis of cerebral malaria. On the other hand, constitutive indoleamine 2,3-dioxygenase expression in the epididymis and the placenta was detected in both C57Bl/6 wild-type and interferon-gamma-/- mice, suggesting a distinct regulatory mechanism for its induction in these normal physiological situations. Although increased indoleamine 2,3-dioxygenase production during murine malaria infection may not by itself cause cerebral pathology, metabolites of the kynurenine pathway may combine with other features of cerebral malaria, such as breakdown of the blood-brain barrier, to influence CNS function and contribute to the symptoms and pathology observed.
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PMID:Increased expression of indoleamine 2,3-dioxygenase in murine malaria infection is predominantly localised to the vascular endothelium. 1554 91

Indoleamine 2,3-dioxygenase (INDO) and tryptophan 2,3-dioxygenase (TDO) each catalyze the first step in the kynurenine pathway of tryptophan metabolism. We describe the discovery of another enzyme with this activity, indoleamine 2,3-dioxygenase-like protein (INDOL1), which is closely related to INDO and is expressed in mice and humans. The corresponding genes have a similar genomic structure and are situated adjacent to each other on human and mouse chromosome 8. They are likely to have arisen by gene duplication before the origin of the tetrapods. The expression of INDOL1 is highest in the mouse kidney, followed by epididymis, and liver. Expression of mouse INDOL1 was further localized to the tubular cells in the kidney and the spermatozoa. INDOL1 was assigned its name because of its structural similarity to INDO. We demonstrate that INDOL1 catalyses the conversion of tryptophan to kynurenine therefore a more appropriate nomenclature for the enzymes might be INDO-1 and INDO-2, or the more commonly-used abbreviations, IDO-1 and IDO-2. Although the two proteins have similar enzymatic activities, their different expression patterns within tissues and during malaria infection, suggests a distinct role for each protein. This identification of INDOL1 may help to explain the regulation of the diversity of physiological and patho-physiological processes in which the kynurenine pathway is involved.
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PMID:Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. 1749 41

The indiscriminate use, abuse and patients' noncompliance to normal prescription of artemisinin and its derivatives are a common practice during the treatment for drug-resistant malaria parasites in most developing countries. This study investigated the influence of artemisinin on the testicular and epididymal sperm antioxidant systems as well as on the plasma levels of hormones from the pituitary and thyroid components of the brain-pituitary-testicular axis. Oral exposure of rats to 0, 7 and 35 mg kg(-1) artemisinin for 7 days showed that the testicular antioxidant status at both therapeutic dose (7 mg kg(-1) ) and overdose (35 mg kg(-1) ), and the sperm antioxidant status at therapeutic dose of artemisinin remained unaffected compared with control. However, increased hydrogen peroxide and lipid peroxidation levels were accompanied by a concomitant decrease in glutathione peroxidase and glutathione-S-transferase activities as well as glutathione level in spermatozoon of rats administered with overdose of artemisinin. While plasma levels of all the hormones investigated remained unaffected, severe epididymal degeneration with concomitant decrease in sperm quantity and quality was observed in rats treated with overdose of artemisinin compared with control. Overall, induction of oxidative stress in the epididymis, but not in the testes, could cause reproductive deficits in individuals unduly undergoing artemisinin therapy.
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PMID:Sperm characteristics, antioxidant status and hormonal profile in rats treated with artemisinin. 2407 12