scholarly journals Orchestrating a heist: uptake and storage of metals by apicomplexan parasites

Microbiology ◽  
2021 ◽  
Vol 167 (12) ◽  
Author(s):  
Megan A. Sloan ◽  
Dana Aghabi ◽  
Clare R. Harding

The acquisition and storage of metals has been a preoccupation of life for millennia. Transition metals, in particular iron, copper and zinc, have vital roles within cells. However, metals also make dangerous cargos; inappropriate uptake or storage of transition metals leads to cell death. This paradox has led to cells developing elegant and frequently redundant mechanisms for fine-tuning local metal concentrations. In the context of infection, pathogens must overcome further hurdles, as hosts act to weaponize metal availability to prevent pathogen colonization and spread. Here, we detail the methods used by the Apicomplexa, a large family of eukaryotic parasites, to obtain and store essential metals.

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Takahito Moriwaki ◽  
Akari Yoshimura ◽  
Yuki Tamari ◽  
Hiroyuki Sasanuma ◽  
Shunichi Takeda ◽  
...  

Abstract Background Peroxiredoxin 1 (PRDX1) is a member of a ubiquitous family of thiol peroxidases that catalyze the reduction of peroxides, including hydrogen peroxide. It functions as an antioxidant enzyme, similar to catalase and glutathione peroxidase. PRDX1 was recently shown act as a sensor of reactive oxygen species (ROS) and play a role in ROS-dependent intracellular signaling pathways. To investigate its physiological functions, PRDX1 was conditionally disrupted in chicken DT40 cells in the present study. Results The depletion of PRDX1 resulted in cell death with increased levels of intracellular ROS. PRDX1-depleted cells did not show the accumulation of chromosomal breaks or sister chromatid exchange (SCE). These results suggest that cell death in PRDX1-depleted cells was not due to DNA damage. 2-Mercaptoethanol protected against cell death in PRDX1-depleted cells and also suppressed elevations in ROS. Conclusions PRDX1 is essential in chicken DT40 cells and plays an important role in maintaining intracellular ROS homeostasis (or in the fine-tuning of cellular ROS levels). Cells deficient in PRDX1 may be used as an endogenously deregulated ROS model to elucidate the physiological roles of ROS in maintaining proper cell growth.


2015 ◽  
Vol 11 (2) ◽  
pp. 173-184 ◽  
Author(s):  
Nafiisa Sobratee ◽  
Tilahun S. Workneh

Abstract Tomato quality is determined by metabolite content which is governed by post-harvest physiological changes. A 30-day full factorial experiment investigated pre-packaging, disinfection and storage temperatures on 18 different biochemical, microbiological, enzymatic and subjective quality attributes of tomato quality. Principal component analysis revealed associations among the variables such as PC1 (28.85%): coliform/enzymatic softening; PC2 (21.52%): free sugars/sweetness; and PC3 (18.20%): sucrose hydrolysis/microbial spoilage/defense metabolites. Discriminant analysis showed that some specific parameters were highly significant (P<0.001) in determining quality changes in relation to the washing procedures and storage temperature. The prominence of ascorbic acid was observed in the equations which discriminate mostly on the basis of microbial deterioration. Further works in this respect entail fine-tuning through model verification of the equations. Multivariate analysis techniques are, therefore, recommended in studies whereby understanding of the phenomenon driving the post-harvest system’s dynamics has to be understood through diverse interrelated metabolic parameters.


2016 ◽  
Vol 46 (8) ◽  
pp. 1997-2007 ◽  
Author(s):  
Jan Däbritz ◽  
Toni Weinhage ◽  
Georg Varga ◽  
Timo Wirth ◽  
Jan M. Ehrchen ◽  
...  

2002 ◽  
Vol 30 (4) ◽  
pp. 766-768 ◽  
Author(s):  
H. Wintz ◽  
T. Fox ◽  
C. Vulpe

Iron, copper and zinc are essential metals for cell metabolism. Plants have evolved different schemes to efficiently mobilize low-solubility nutrients such as metals from their environment and to transport them between organs. In this review we highlight the divergences and convergences of the iron, copper and zinc uptake, transport and homoeostatic pathways.


2021 ◽  
Author(s):  
Augustine George ◽  
Mohan Indhu ◽  
Sundarapandian Ashokraj ◽  
Ganesh Shanmugam ◽  
Ponesakki Ganesan ◽  
...  

Abstract The newly developed molecular biology approach expanding the genetic code was used to incorporate the non-canonical amino acid dihydroxyphenylalanine for fine-tuning of proteins. Further, the congener protein was enzymatically converted to form quinone for strain promoted click chemistry. The reaction yields a single product with defined stereochemistry and temporally controlled conjugation with bicyclonon[6.1.0]-4-yne (BCN) as well as dibenzocyclooctyne-PEG-Fluor 545. The promising bioconjugation of congener protein with dibenzocyclooctyne-PEG-Fluor 545 was used as a fluorescent marker for selective cell imaging and detection of programmed cell death in EAhy926 cells.


2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Barbara Schroeder ◽  
Travis Vander Steen ◽  
Ingrid Espinoza ◽  
Chandra M. Kurapaty Venkatapoorna ◽  
Zeng Hu ◽  
...  

AbstractInhibitors of the lipogenic enzyme fatty acid synthase (FASN) have attracted much attention in the last decade as potential targeted cancer therapies. However, little is known about the molecular determinants of cancer cell sensitivity to FASN inhibitors (FASNis), which is a major roadblock to their therapeutic application. Here, we find that pharmacological starvation of endogenously produced FAs is a previously unrecognized metabolic stress that heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors. Evaluation of the death decision circuits controlled by the BCL-2 family of proteins revealed that FASN inhibition is accompanied by the upregulation of the pro-death BH3-only proteins BIM, PUMA, and NOXA. Cell death triggered by FASN inhibition, which causally involves a palmitate/NADPH-related redox imbalance, is markedly diminished by concurrent loss of BIM or PUMA, suggesting that FASN activity controls cancer cell survival by fine-tuning the BH3 only proteins-dependent mitochondrial threshold for apoptosis. FASN inhibition results in a heightened mitochondrial apoptosis priming, shifting cells toward a primed-for-death state “addicted” to the anti-apoptotic protein BCL-2. Accordingly, co-administration of a FASNi synergistically augments the apoptosis-inducing activity of the dual BCL-XL/BCL-2 inhibitor ABT-263 (navitoclax) and the BCL-2 specific BH3-mimetic ABT-199 (venetoclax). FASN inhibition, however, fails to sensitize breast cancer cells to MCL-1- and BCL-XL-selective inhibitors such as S63845 and A1331852. A human breast cancer xenograft model evidenced that oral administration of the only clinically available FASNi drastically sensitizes FASN-addicted breast tumors to ineffective single-agents navitoclax and venetoclax in vivo. In summary, a novel FASN-driven facet of the mitochondrial priming mechanistically links the redox-buffering mechanism of FASN activity to the intrinsic apoptotic threshold in breast cancer cells. Combining next-generation FASNis with BCL-2-specific BH3 mimetics that directly activate the apoptotic machinery might generate more potent and longer-lasting antitumor responses in a clinical setting.


2007 ◽  
pp. 78-125 ◽  
Author(s):  
R. R. Crichton ◽  
J.-C. Mareschal

1995 ◽  
Vol 05 (01) ◽  
pp. 27-32 ◽  
Author(s):  
I. SATO ◽  
N. MATSUSAKA ◽  
H. KOBAYASHI ◽  
T. SUZUKI ◽  
K. SERA ◽  
...  

Ca-DTPA and Zn-DTPA were injected intraperitoneally into rats with a dose of 30 or 300 µmol/kg. The blood was collected from the tail vein just before the injection, 3, 6 and 24 hours after the injection. and centrifuged 10 separate the plasma. These plasma samples were analyzed by PIXE at Nishina Memorial Cyclotron Center. Sodium, potassium, calcium, iron, copper and zinc were detected in the plasma. Ca-DTPA significantly lowered the concentration of zinc, while no significant changes were observed in the other metals. Zn-DTPA did not lower any metal concentrations, but a significant increase of plasma zinc was observed. In conclusion, Ca-DTPA was confirmed to induce hypozincemia, which may be the cause of fetal injuries such as abortion, fetal death and malformation. Zn-DTPA was suggested not to induce any deficiencies of essential metals.


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