Influence of NO Synthase Inhibitor L-NAME on Parasitemia and Survival of &lt;i&gt;Plasmodium berghei&lt;/i&gt; Infected Mice

Koka, Saisudha; Lang, Camelia; Niemoeller, Olivier M.; Boini, Krishna M.; Nicolay, Jan P.; Huber, Stephan M.; Läng, Florian

doi:10.1159/000129641

Cited by 77 publications

(60 citation statements)

References 70 publications

(79 reference statements)

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“…A wide variety of clinical disorders is known to stimulate eryptosis, including iron deficiency [36], phosphate depletion [6], hemolytic uremic syndrome [43], sepsis [35], malaria [10,37,38], or Wilson's disease [46]. Some of these diseases may cause eryptosis by stimulating the formation of hemin.…”

Section: Discussionmentioning

confidence: 99%

Hemin-induced suicidal erythrocyte death

2009

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Several diseases, such as malaria, sickle cell disease, and ischemia/reperfusion may cause excessive formation of hemin, which may in turn trigger hemolysis. A variety of drugs and diseases leading to hemolysis triggers suicidal erythrocyte death or eryptosis, i.e., cell membrane scrambling and cell shrinkage. Eryptosis is elicited by increased cytosolic Ca 2+ activity and by ceramide. The present study explored whether hemin stimulates eryptosis. Cell membrane scrambling was estimated from annexin Vbinding to phosphatidylserine exposed at the cell surface, cell shrinkage from forward scatter in fluorescence-activated cell sorter analysis, cytosolic Ca 2+ activity from Fluo3 fluorescence and ceramide formation from fluorescencelabeled antibody binding. Exposure to hemin (1-10 μM) within 48 h significantly increased annexin V-binding, decreased forward scatter, increased cytosolic Ca 2+ activity, and stimulated ceramide formation. In conclusion, hemin stimulates suicidal cell death, which may in turn contribute to the clearance of circulating erythrocytes and thus to anemia.

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Section: Discussionmentioning

confidence: 99%

Hemin-induced suicidal erythrocyte death

2009

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“…There is conflicting evidence regarding the role of NO in the process of resistance against malaria parasites. Schizonts treated in vitro with NO donors caused a delayed infection to mice in a dose and time-dependent manner, which, suggest an inhibitory role for NO [58] with influence on parasitemia and survival of Plasmodium berghei in infected mice [59] or P. berghei Anka in rats [60]. Moreover, human severe malaria is associated with decreased NO production [61] and iNOS variants in regions of differing disease manifestation [62].…”

Section: Plasmodium Spmentioning

confidence: 96%

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

Nahrevanian

2009

Braz J Infect Dis

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Nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions and signaling pathways. The NO synthase (NOS) enzyme family consists of three major isoforms, which convey variety of messages between cells, including signals for vasorelaxation, neurotransmission and cytotoxicity. This family of enzymes are generally classified as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Increased levels of NO are induced from iNOS during infection; while eNOS and nNOS may be produced at the baseline in normal conditions. An association of some key cytokines appears to be essential for NOS gene regulation in the immunity of infections. Accumulating evidence indicates that parasitic diseases are commonly associated with elevated production of NO. NO plays a role in the immunoregulation and it is implicated in the host non-specific defence in a variety of infections. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial. In the present review, the role of parasitic infections will be discussed in the controversy related to the NO production and iNOS gene expression in different parasites and a variety of experimental models.

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“…The accelerated eryptosis in sickle-cell trait, beta-thalassaemia trait, Hb-C deficiency and G6PD deficiency leads to clearance of infected erythrocytes which counteracts parasitemia and protects against a severe course of malaria [46,[96][97][98]. Parasitemia and clinical course of malaria are further favourably influenced by triggering eryptosis with iron deficiency [99] and treatment with lead [99], chlorpromazine [100] or NO synthase inhibitors [100]. Possibly, the antimalarial effects of nigericin [27] include stimulation of eryptosis of Plasmodium-infected erythrocytes.…”

Section: Discussionmentioning

confidence: 99%

Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin

Bissinger

Malik

Bouguerra

et al. 2015

Basic Clin Pharma Tox

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The K + ,H + ionophore and antibiotic nigericin has been shown to trigger apoptosis and is thus considered for the treatment of malignancy. Cellular mechanisms involved include induction of oxidative stress, which is known to activate erythrocytic Ca 2+ -permeable unselective cation channels leading to Ca 2+ entry, increase in cytosolic Ca 2+ activity ([Ca 2+ ] i ) and subsequent stimulation of eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. This study explored whether and how nigericin induces eryptosis. Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca 2+ ] i from Fluo3 fluorescence, pH i from BCECF fluorescence, ceramide abundance utilizing antibodies and reactive oxygen species (ROS) formation from DCFDA-dependent fluorescence. A 48-hr exposure of human erythrocytes to nigericin significantly increased the percentage of annexin-V-binding cells (0.1-10 nM), significantly decreased forward scatter (0.1-1 nM), significantly decreased cytosolic pH (0.1-1 nM) and significantly increased Fluo3 fluorescence (0.1-10 nM). Nigericin (1 nM) slightly, but significantly, increased ROS, but did not significantly modify ceramide abundance. Materials and MethodsErythrocytes, solutions and chemicals. Li-heparin-anticoagulated fresh blood samples were kindly provided by the blood bank of the University of T€ ubingen. The study was approved by the ethics committee of the University of T€ ubingen (184/2003 V). The blood was centrifuged at 120 9 g for 20 min. at 21°C and the platelet-and leucocyte-containing supernatant were disposed. Erythrocytes were incubated in vitro at a haematocrit of 0.4% in Ringer solution containing (in mM) 125 NaCl, 5 KCl, 1 MgSO 4 , 32 N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (HEPES; pH 7.4), 5 glucose and 1 CaCl 2 , at 37°C for 48 hr. Where indicated, erythrocytes were exposed to nigericin (Enzo Life Sciences, L€ orrach, Germany) at the indicated concentrations.Annexin V binding and forward scatter. After incubation under the respective experimental condition, a 150-ll cell suspension was centrifuged at 350 rcf for 3 min. and, after trashing the supernatant,

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Influence of NO Synthase Inhibitor L-NAME on Parasitemia and Survival of <i>Plasmodium berghei</i> Infected Mice

Cited by 77 publications

References 70 publications

Hemin-induced suicidal erythrocyte death

Hemin-induced suicidal erythrocyte death

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin

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