Inhibition of EIF-5A prevents apoptosis in human cardiomyocytes after malaria infection

Kaiser, Annette; Heiß, Kirsten; Mueller, Ann‐Kristin; Fimmers, Rolf; Matthes, Jan; Njuguna, James Thujon

doi:10.1007/s00726-020-02843-2

Cited by 9 publications

(3 citation statements)

References 58 publications

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“…An in vitro model of malaria infection in human cardiomyocytes determined that reduction of hyp-eIF5A levels by GC7 treatment leads to a decrease in the release of cytochrome c and lactate from damaged mitochondria and reduces proinflammatory and pro-apoptotic myocardial caspase-1 activity. These results demonstrate that the administration of GC7 in a malaria-simulating in vitro model prevents cardiac damage driven by hypoxia [129].…”

Section: Links Between Eif5a and Mitochondrial Functionmentioning

confidence: 60%

Role of eIF5A in Mitochondrial Function

Barba‐Aliaga

Alepuz

2022

IJMS

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The eukaryotic translation initiation factor 5A (eIF5A) is an evolutionarily conserved protein that binds ribosomes to facilitate the translation of peptide motifs with consecutive prolines or combinations of prolines with glycine and charged amino acids. It has also been linked to other molecular functions and cellular processes, such as nuclear mRNA export and mRNA decay, proliferation, differentiation, autophagy, and apoptosis. The growing interest in eIF5A relates to its association with the pathogenesis of several diseases, including cancer, viral infection, and diabetes. It has also been proposed as an anti-aging factor: its levels decay in aged cells, whereas increasing levels of active eIF5A result in the rejuvenation of the immune and vascular systems and improved brain cognition. Recent data have linked the role of eIF5A in some pathologies with its function in maintaining healthy mitochondria. The eukaryotic translation initiation factor 5A is upregulated under respiratory metabolism and its deficiency reduces oxygen consumption, ATP production, and the levels of several mitochondrial metabolic enzymes, as well as altering mitochondria dynamics. However, although all the accumulated data strongly link eIF5A to mitochondrial function, the precise molecular role and mechanisms involved are still unknown. In this review, we discuss the findings linking eIF5A and mitochondria, speculate about its role in regulating mitochondrial homeostasis, and highlight its potential as a target in diseases related to energy metabolism.

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Section: Links Between Eif5a and Mitochondrial Functionmentioning

confidence: 60%

Role of eIF5A in Mitochondrial Function

Barba‐Aliaga

Alepuz

2022

IJMS

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“…Many of these molecules promote vasculature occlusion for inducing inflammation and endothelial cell activation and induce acute-phase responses to prevent the spread of malaria. Routine laboratory results indicate liver and kidney dysfunction ( Nieman et al., 2009 ; Nantakomol et al., 2011 ; Mita-Mendoza et al., 2013 ; Mangal et al., 2017 ; Cheaveau et al., 2019; Dinkar et al., 2020 ; Khrapunov et al., 2021 ; Tona Lutete et al., 2021 ; Megabiaw et al., 2022 ), and in some cases, abnormal myocardial enzyme is reported ( Herr et al., 2011 ; Dinkar et al., 2020 ; Kaiser et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Biochemical characteristics of patients with imported malaria

Lin

Luo

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectivesThis study aimed to investigate the clinical and biochemical profiles of patients with imported malaria infection between 1 January 2011 and 30 April 2022 and admitted to the Fourth People’s Hospital of Nanning.MethodsThis cohort study enrolled 170 patients with conformed imported malaria infection. The clinical and biochemical profiles of these participants were analyzed with malaria parasite clearance, and signs and symptoms related to malaria disappearance were defined as the primary outcome. A multivariable logistic regression model was used to evaluate the odds ratios (ORs) with 95% confidence intervals (CIs) for cerebral malaria. The Cox model was used to estimate the hazard ratios (HRs) with 95% CIs for parasite clearance.ResultsAdenosine deaminase and parasitemia were found to be independent risk factors for severe malaria in patients with imported malaria (OR = 1.0088, 95% CI: 1.0010–1.0167, p = 0.0272 and OR = 2.0700, 95% CI: 1.2584–3.4050, p = 0.0042, respectively). A 0.5–standard deviation (SD) increase of variation for urea (HR = 0.6714, 95% CI: 0.4911–0.9180), a 0.5-SD increase of variation for creatinine (HR = 0.4566, 95% CI: 0.2762–0.7548), a 0.25-SD increase of variation for albumin (HR = 0.4947, 95% CI: 0.3197–0.7653), a 0.25-SD increase of variation for hydroxybutyrate dehydrogenase (HR = 0.6129, 95% CI: 0.3995–0.9402), and a 1.0-SD increase of variation for ferritin (HR = 0.5887, 95% CI: 0.3799–0.9125) were associated with a higher risk for increased parasite clearance duration than a low-level change.ConclusionsAspartate aminotransferase, urea, creatinine, albumin, hydroxybutyrate dehydrogenase, and ferritin are useful biochemical indicators in routine clinical practice to evaluate prognosis for imported malaria.

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“…Moreover, MC administration leads to mitochondrial dysfunction leading to apoptosis in cancer cells [ 7 ]. Recently, it was shown that inhibition of EIF-5A induces apoptosis in cardiomyocytes after malaria infection [ 77 ] via tyrosine sulfation of the protein [ 78 ]. Collectively, the data show that Hsps and hypusinated eIF5A exhibit antiapoptotic effects.…”

Section: Hsp Inhibitors Of Anticancer Chemotherapy Might Be Useful Fo...mentioning

confidence: 99%

An Undefined Interaction between Polyamines and Heat Shock Proteins Leads to Cellular Protection in Plasmodium falciparum and Proliferating Cells in Various Organisms

et al. 2023

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Environmental stimuli can distress the internal reaction of cells and their normal function. To react promptly to sudden environmental changes, a cascade of heat shock proteins (Hsps) functions to protect and act as housekeepers inside the cells. In parallel to the heat shock response, the metabolic polyamine (PA) status changes. Here, we discuss possible ways of putative interactions between Hsps and polyamines in a wide lineage of eukaryotic model organisms with a particular focus on parasitic protozoa such as Plasmodium falciparum (P. falciparum). The supposed interaction between polyamines and Hsps may protect the parasite from the sudden change in temperature during transmission from the female Anopheles mosquito to a human host. Recent experiments performed with the spermidine mimetic inhibitor 15-deoxyspergualine in Plasmodium in vitro cultures show that the drug binds to the C-terminal EEVD motif of Hsp70. This leads to inhibition of protein biosynthesis caused by prevention of eIF5A2 phosphorylation and eukaryotic initiation factor 5A (eIF5A) modification. These observations provide further evidence that PAs are involved in the regulation of protein biosynthesis of Hsps to achieve a protective effect for the parasite during transmission.

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Inhibition of EIF-5A prevents apoptosis in human cardiomyocytes after malaria infection

Cited by 9 publications

References 58 publications

Role of eIF5A in Mitochondrial Function

Role of eIF5A in Mitochondrial Function

Biochemical characteristics of patients with imported malaria

An Undefined Interaction between Polyamines and Heat Shock Proteins Leads to Cellular Protection in Plasmodium falciparum and Proliferating Cells in Various Organisms

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