31P MRS analysis of the phospholipid composition of the peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) of patients with acute leukemia (AL)

Kuliszkiewicz‐Janus, Małgorzata; Tuz, Mariusz Adam; Kiełbiński, Marek; Jaźwiec, Bożena; Niedoba, Joanna; Baczyński, Stanisław

doi:10.2478/s11658-008-0032-7

Cited by 10 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rather small increase in ζ upon addition of MP-1 to PCCol vesicles confirms the poor binding, and the flatness of the ζ potential curves suggests that <1 μM peptide is enough to hinder further binding. Those results are in accordance with the fact that cholesterol affects the fluidity and the dipole potential of phospholipid membranes, 40 inducing the ordering of the acyl chain region. 41 In this way, the attenuation of the porelike activity of PCCol bilayers can be correlated with the increase in the compressibility and bending modulii, hampering lytic activity.…”

Section: ■ Discussionsupporting

confidence: 90%

Influence of the Bilayer Composition on the Binding and Membrane Disrupting Effect of Polybia-MP1, an Antimicrobial Mastoparan Peptide with Leukemic T-Lymphocyte Cell Selectivity

et al. 2012

View full text Add to dashboard Cite

This study shows that MP-1, a peptide from the venom of the Polybia paulista wasp, is more toxic to human leukemic T-lymphocytes than to human primary lymphocytes. By using model membranes and electrophysiology measurements to investigate the molecular mechanisms underlying this selective action, the porelike activity of MP-1 was identified with several bilayer compositions. The highest average conductance was found in bilayers formed by phosphatidylcholine or a mixture of phosphatidylcholine and phosphatidylserine (70:30). The presence of cholesterol or cardiolipin substantially decreases the MP-1 pore activity, suggesting that the membrane fluidity influences the mechanism of selective toxicity. The determination of partition coefficients from the anisotropy of Trp indicated higher coefficients for the anionic bilayers. The partition coefficients were found to be 1 order of magnitude smaller when the bilayers contain cholesterol or a mixture of cholesterol and sphingomyelin. The blue shift fluorescence, anisotropy values, and Stern-Volmer constants are indications of a deeper penetration of MP-1 into anionic bilayers than into zwitterionic bilayers. Our results indicate that MP-1 prefers to target leukemic cell membranes, and its toxicity is probably related to the induction of necrosis and not to DNA fragmentation. This mode of action can be interpreted considering a number of bilayer properties like fluidity, lipid charge, and domain formation. Cholesterol-containing bilayers are less fluid and less charged and have a tendency to form domains. In comparison to healthy cells, leukemic T-lymphocyte membranes are deprived of this lipid, resulting in decreased peptide binding and lower conductance. We showed that the higher content of anionic lipids increases the level of binding of the peptide to bilayers. Additionally, the absence of cholesterol resulted in enhanced pore activity. These findings may drive the selective toxicity of MP-1 to Jurkat cells.

show abstract

Section: ■ Discussionsupporting

confidence: 90%

Influence of the Bilayer Composition on the Binding and Membrane Disrupting Effect of Polybia-MP1, an Antimicrobial Mastoparan Peptide with Leukemic T-Lymphocyte Cell Selectivity

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Other anionic lipid species such as phosphatidylglycerol (PG), phosphatidic acid (PA), phosphatidylserine (PS), phosphatidylinositol (PI) and cardiolipin are also present at variable, and generally much higher, concentrations in native membranes 13 14 . Membrane lipid composition can vary under different physiological and pathological conditions 15 16 17 , and has been invoked causally in various diseases conditions 18 19 20 . However, progress in understanding the role of specific lipids in controlling of membrane protein function has been limited 21 because they cannot be readily manipulated in native membranes.…”

mentioning

confidence: 99%

Secondary anionic phospholipid binding site and gating mechanism in Kir2.1 inward rectifier channels

et al. 2013

View full text Add to dashboard Cite

Inwardly rectifying potassium (Kir) channels regulate multiple tissues. All Kir channels require interaction of phosphatidyl-4,5-bisphosphate (PIP2) at a crystallographically identified binding site, but an additional nonspecific secondary anionic phospholipid (PL(−)) is required to generate high PIP2 sensitivity of Kir2 channel gating. The PL(−)-binding site and mechanism are yet to be elucidated. Here we report docking simulations that identify a putative PL(−)-binding site, adjacent to the PIP2-binding site, generated by two lysine residues from neighbouring subunits. When either lysine is mutated to cysteine (K64C and K219C), channel activity is significantly decreased in cells and in reconstituted liposomes. Directly tethering K64C to the membrane by modification with decyl-MTS generates high PIP2 sensitivity in liposomes, even in the complete absence of PL(−)s. The results provide a coherent molecular mechanism whereby PL(−) interaction with a discrete binding site results in a conformational change that stabilizes the high-affinity PIP2 activatory site.

show abstract

“…These differences were reproduced in individual cancers with statistical significance reaching in BrC and CLL for respectively PC and PE levels. The previously published findings on the changes in PC and PE fractions are very diverse and sometimes controversial [39,40,41]. For example, substantial evidence suggests that PC levels are elevated during cancers, whereas significant decrease was noted in breast cancer cell lines [42].…”

Section: Discussionmentioning

confidence: 99%

Similarities in Blood Mononuclear Cell Membrane Phospholipid Profiles during Malignancy

et al. 2018

View full text Add to dashboard Cite

Phospholipids (PLs), key elements of cellular membranes, are regulated reciprocally with membrane proteins and can act as sensors for alterations in physiological or pathological states of cells including initiation and development of cancer. On the other hand, peripheral blood mononuclear cells (MNCs) play an important role in antitumor immune response by reacting to cancerous modifications in distant organs. In the current study, we tested the hypothesis that tumor initiation and development are reflected in the alteration pattern of the MNC PL component. We analyzed MNC membrane PL fractions in samples from healthy individuals and from patients with diverse types of cancers to reveal possible alterations induced by malignancy. Compared to healthy controls, the cancer samples demonstrated shifts in several membrane PL profiles. In particular, when analyzing cancer data pooled together, there were significantly higher levels in lysophosphatidylcholine, phosphatidylcholine, and phosphatidylethanolamine fractions, and significantly lower quantities in phosphatidylinositol, phosphatidylserine, and phosphatidic acid fractions in cancer samples compared to controls. The levels of sphingomyelins and diphosphatidylglycerols were relatively unaffected. Most of the differences in PLs were sustained during the analysis of individual cancers such as breast cancer and chronic lymphocytic leukemia. Our findings suggest the presence of a common pattern of changes in MNC PLs during malignancy.

show abstract

31P MRS analysis of the phospholipid composition of the peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) of patients with acute leukemia (AL)

Cited by 10 publications

References 21 publications

Influence of the Bilayer Composition on the Binding and Membrane Disrupting Effect of Polybia-MP1, an Antimicrobial Mastoparan Peptide with Leukemic T-Lymphocyte Cell Selectivity

Influence of the Bilayer Composition on the Binding and Membrane Disrupting Effect of Polybia-MP1, an Antimicrobial Mastoparan Peptide with Leukemic T-Lymphocyte Cell Selectivity

Secondary anionic phospholipid binding site and gating mechanism in Kir2.1 inward rectifier channels

Similarities in Blood Mononuclear Cell Membrane Phospholipid Profiles during Malignancy

Contact Info

Product

Resources

About