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Role of the lipoperoxidation product 4-hydroxynonenal in the pathogenesis of severe malaria anemia and malaria immunodepression.

Schwarzer E, Arese P, Skorokhod OA - Oxid Med Cell Longev (2015)

Bottom Line: Complications are associated with oxidative stress and lipoperoxidation.Its final product 4-hydroxynonenal (4-HNE), a stable yet very reactive and diffusible molecule, forms covalent conjugates with proteins, DNA, and phospholipids and modulates important cell functions at very low concentrations.Data from other diseases qualify 4-HNE both as oxidative stress marker and as pathomechanistically important molecule.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, University of Torino, Via Santena 5 Bis, 10126 Torino, Italy.

ABSTRACT
Oxidative stress plays an important role in the pathogenesis of falciparum malaria, a disease still claiming close to 1 million deaths and 200 million new cases per year. Most frequent complications are severe anemia, cerebral malaria, and immunodepression, the latter being constantly present in all forms of malaria. Complications are associated with oxidative stress and lipoperoxidation. Its final product 4-hydroxynonenal (4-HNE), a stable yet very reactive and diffusible molecule, forms covalent conjugates with proteins, DNA, and phospholipids and modulates important cell functions at very low concentrations. Since oxidative stress plays important roles in the pathogenesis of severe malaria, it appears important to explore the role of 4-HNE in two important malaria complications such as malaria anemia and malaria immunodepression where oxidative stress is considered to be involved. In this review we will summarize data about 4-HNE chemistry, its biologically relevant chemical properties, and its role as regulator of physiologic processes and as pathogenic factor. We will review studies documenting the role of 4-HNE in severe malaria with emphasis on malaria anemia and immunodepression. Data from other diseases qualify 4-HNE both as oxidative stress marker and as pathomechanistically important molecule. Further studies are needed to establish 4-HNE as accepted pathogenic factor in severe malaria.

No MeSH data available.


Related in: MedlinePlus

4-HNE source in malaria.
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fig3: 4-HNE source in malaria.

Mentions: During its development the malaria parasite digests the major part of host RBC hemoglobin and polymerizes the undigested and prooxidant heme to HZ (hemozoin, malaria pigment) in close contact with the membrane of the digestive vacuole of the parasite [47]. Similar to free heme, isolated HZ catalyzes in vitro the peroxidation of PUFAs with subsequent degradation to 4-HNE and other products (Figures 1 and 2 and [48]). The onset of hemoglobin degradation and HZ formation at young trophozoite stage coincided with a significantly enhanced formation of 4-HNE and 4-HNE-membrane protein conjugates in parasitized RBCs, compared to nonparasitized control RBCs. The progressive HZ generation during parasite growth was accompanied by the increase of 4-HNE conjugates up to 15-fold higher levels in HZ-rich schizonts compared to young HZ-free ring-forms (Figure 3). The conjugates can be detected and quantified by flow cytometry or fluorescence microscopy after recognition by specific antibodies [11, 49, 50]. 4-HNE conjugates are not confined to 4-HNE-producing cells but were also found in nonparasitized RBCs (npRBCs) cytoadherent to trophozoites (see Figure 4) [51].


Role of the lipoperoxidation product 4-hydroxynonenal in the pathogenesis of severe malaria anemia and malaria immunodepression.

Schwarzer E, Arese P, Skorokhod OA - Oxid Med Cell Longev (2015)

4-HNE source in malaria.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4417603&req=5

fig3: 4-HNE source in malaria.
Mentions: During its development the malaria parasite digests the major part of host RBC hemoglobin and polymerizes the undigested and prooxidant heme to HZ (hemozoin, malaria pigment) in close contact with the membrane of the digestive vacuole of the parasite [47]. Similar to free heme, isolated HZ catalyzes in vitro the peroxidation of PUFAs with subsequent degradation to 4-HNE and other products (Figures 1 and 2 and [48]). The onset of hemoglobin degradation and HZ formation at young trophozoite stage coincided with a significantly enhanced formation of 4-HNE and 4-HNE-membrane protein conjugates in parasitized RBCs, compared to nonparasitized control RBCs. The progressive HZ generation during parasite growth was accompanied by the increase of 4-HNE conjugates up to 15-fold higher levels in HZ-rich schizonts compared to young HZ-free ring-forms (Figure 3). The conjugates can be detected and quantified by flow cytometry or fluorescence microscopy after recognition by specific antibodies [11, 49, 50]. 4-HNE conjugates are not confined to 4-HNE-producing cells but were also found in nonparasitized RBCs (npRBCs) cytoadherent to trophozoites (see Figure 4) [51].

Bottom Line: Complications are associated with oxidative stress and lipoperoxidation.Its final product 4-hydroxynonenal (4-HNE), a stable yet very reactive and diffusible molecule, forms covalent conjugates with proteins, DNA, and phospholipids and modulates important cell functions at very low concentrations.Data from other diseases qualify 4-HNE both as oxidative stress marker and as pathomechanistically important molecule.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, University of Torino, Via Santena 5 Bis, 10126 Torino, Italy.

ABSTRACT
Oxidative stress plays an important role in the pathogenesis of falciparum malaria, a disease still claiming close to 1 million deaths and 200 million new cases per year. Most frequent complications are severe anemia, cerebral malaria, and immunodepression, the latter being constantly present in all forms of malaria. Complications are associated with oxidative stress and lipoperoxidation. Its final product 4-hydroxynonenal (4-HNE), a stable yet very reactive and diffusible molecule, forms covalent conjugates with proteins, DNA, and phospholipids and modulates important cell functions at very low concentrations. Since oxidative stress plays important roles in the pathogenesis of severe malaria, it appears important to explore the role of 4-HNE in two important malaria complications such as malaria anemia and malaria immunodepression where oxidative stress is considered to be involved. In this review we will summarize data about 4-HNE chemistry, its biologically relevant chemical properties, and its role as regulator of physiologic processes and as pathogenic factor. We will review studies documenting the role of 4-HNE in severe malaria with emphasis on malaria anemia and immunodepression. Data from other diseases qualify 4-HNE both as oxidative stress marker and as pathomechanistically important molecule. Further studies are needed to establish 4-HNE as accepted pathogenic factor in severe malaria.

No MeSH data available.


Related in: MedlinePlus