Coordinated Stage-Dependent Enhancement of Plasmodium falciparum Antioxidant Enzymes and Heat Shock Protein Expression

Strategic Insights -

A recent study from the University of Turin in Italy has shed light on the complex mechanisms of Plasmodium falciparum, the parasite responsible for falciparum malaria. The researchers, led by O.B. Akidendunge, found that antioxidant enzymes and heat shock proteins (HSPs) play a crucial role in the parasite's survival and growth. Their study, published in Malaria Journal, suggests that disrupting these systems could provide new avenues for anti-malaria therapy.

Key Takeaways:

  • The mRNA expression of antioxidant enzymes and HSPs in P. falciparum displayed coordinated stage-dependent modulation, being low at ring, highest at early trophozoite, and again very low at schizont stage.
  • Additional exogenous oxidative stress or growth in antioxidant-blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs.
  • Protein expression of antioxidant enzymes was also increased in oxidatively-stressed trophozoites.
  • Results indicated that mRNA expression of parasite antioxidant enzymes and HSPs was redox-responsive and showed remarkably increased and co-ordinated expression in oxidatively-stressed parasites and in parasites growing in antioxidant-blunted G6PD-deficient RBCs.
  • The researchers concluded that the inclusion of anti-HSP molecules in anti-malarial combined drugs may be a promising approach.
  • P. falciparum antioxidant enzymes and HSPs were found to be stage-dependent and redox-responsive, allowing the parasite to adapt to changing environments.
  • Several antimalarials increase oxidative stress or block antioxidant defense in the parasitized RBC, making it a potential target for disruption.
  • The study provides new perspectives for anti-malaria therapy based on the joint disruption of the parasite antioxidant enzymes/HSP system.

Statistics:

  • 10 representative P. falciparum antioxidant enzymes and hsp60/70-2/70-3/75/90 were studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, RBCs oxidatively-stressed by moderate H2O2 generation, and in G6PD-deficient RBCs.
  • The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane.
  • mRNA expression of antioxidant enzymes and HSPs displayed coordinated stage-dependent modulation, being low at ring (20%), highest at early trophozoite (60%), and again very low at schizont stage (10%).

Sources:

  • Akidendunge, O.B., et al. (2009). Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells. Malaria Journal, 8(), 113.
  • Falciparum Malaria
  • University of Turin, Dept. of Genetics Biology & Biochemistry, School Medical, Turin, Italy.