Phospholipid Composition and Electric Charge in Healthy and Cancerous Parts of Human Kidneys

Szachowicz-Petelska, Barbara; Dobrzyńska, Izabela; Skrodzka, Marta; Darewicz, Barbara; Figaszewski, Zbigniew A.; Kudelski, Jacek

doi:10.1007/s00232-013-9554-7

Cited by 37 publications

(32 citation statements)

References 24 publications

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“…Our previous experiments demonstrated that the cell membrane and the function are modified during cancer transformation. It is reflected by changes in the amount of phospholipids of human renal cell membrane [1]. The results of our research confirm the increase in the levels of phospholipids of renal cancer cell membrane relative to the unmodified cells (Figure 3).…”

Section: Discussionsupporting

confidence: 84%

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Changes in the Physico-Chemical Properties of Human Kidney Cell Membranes during the Cancer Transformation

Szachowicz-Petelska¹,

Dobrzyńska²,

Figaszewski³

et al. 2014

ABC

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Kidney tissue is particularly susceptible to reactive oxygen species attack which leads to development of cancer. During oxidative stress, membrane lipids and proteins are major targets of reactive oxygen species (ROS). This work is focused on changes of phospholipids, proteins content and electric charge that occur in cell membranes of kidney cancer of pT3 stage, grade G3 and with metastasis. Qualitative and quantitative phospholipid composition and the presence of integral membrane proteins were determined by high-performance liquid chromatography. Electrophoresis was used to determine the surface charge density of the human kidney cell membrane. It was shown that the process of cancer transformation was accompanied by an increase phospholipid levels and altered the level of integral proteins as determined by decrease phenylalanine, tyrosine, cysteine and arginine. Moreover, the process of cancer transformation significantly enhanced changes in the surface charge density of the human kidney cell membrane. Cell membrane structure and function are modified by neoplasm lesion.

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Section: Discussionsupporting

confidence: 84%

“…portant properties of a biological membrane are its electric charge and its potential drop between the membrane and surrounding solution. Electric properties of the membrane are determined by acid-base and complex formation equilibria of membrane and solution components [1]. Most membrane components-phospholipids and proteins-are involved in those equilibria.…”

mentioning

confidence: 99%

Changes in the Physico-Chemical Properties of Human Kidney Cell Membranes during the Cancer Transformation

Szachowicz-Petelska¹,

Dobrzyńska²,

Figaszewski³

et al. 2014

ABC

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“…[10][11][12] Moreover, there have been no studies comprehensively evaluating anionic lipids using clinical RCC samples. [10][11][12] A MALDI matrix is selective for ionization of certain molecule groups. Our DHB/CHCA binary matrix-based tissue MALDI-MS analysis is optimized for charged lipids, not for neutral lipids such as TAG.…”

Section: Resultsmentioning

confidence: 99%

“…Our study demonstrates that profiling of lipid other than TAGs may be useful for distinguishing RCC tissue from normal tissue samples and for classifying RCC according to its histology. There have been several studies evaluating the lipid profiles of RCC, but previous studies are limited by small sample size . Moreover, there have been no studies comprehensively evaluating anionic lipids using clinical RCC samples …”

Section: Discussionmentioning

confidence: 99%

Low C24‐OH and C22‐OH sulfatides in human renal cell carcinoma

et al. 2014

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Histopathologic diagnosis of renal cell carcinoma (RCC) may sometimes be difficult with small biopsy samples. We applied histology-directed matrix-assisted laser desorption/ionization mass spectrometry to RCC samples to evaluate whether and how lipid profiles are different between RCC and normal tissue. We evaluated 59 RCC samples and 24 adjacent normal tissue samples collected from patients who underwent surgery. Five peaks were significantly differently expressed (p < 10(-7)) between RCCs and adjacent normal tissue samples. C24-OH sulfatide (ST-OH {18:1/24:0}[M-H](-); m/z 906.7 in the negative ion mode) and C22-OH sulfatide (ST-OH {18:1/22:0}[M-H](-); m/z 878.6 in the negative ion mode) were most significantly underexpressed in RCC samples, compared with adjacent normal tissue samples. With 100 random training-to-test partitions within these samples, the median prediction accuracy (RCC vs. normal) ranged from 96.3% to 100% at p cutoff values for feature selection ranging from 0.001 to 10(-7). Two oncocytoma samples were predicted as normal tissue by five lipids that were differentially expressed between RCC and normal tissue at p < 10(-7). Clear-cell, papillary, and chromophobe RCCs were different in lipid profiles. Permutation p- values for 0.632+ bootstrap cross-validated misclassification rates were less than 0.05 for all the classifiers. Thus, lipid profiles differentiate RCC from normal tissue and may possibly classify the histology of RCC.

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“…Evidence has accrued that PC, the major phospholipid component of eukaryotic membranes, contributes to both proliferative growth and programmed cell death. On the one hand, the PC content was shown to increase with cell transformation and tumor progression (35)(36)(37)(38). However, on the other hand, PC…”

Section: Ohoa Is Not a Sms Activatormentioning

confidence: 99%

2-Hydroxy-oleic acid does not activate sphingomyelin synthase activity

Lou

Liu

Hou

et al. 2018

Journal of Biological Chemistry

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Edited by George M. Carman 2-Hydroxy-oleic acid (2OHOA) is a potent anticancer drug that induces cancer cell cycle arrest and apoptosis. Previous studies have suggested that 2OHOA's anticancer effect is mediated by SMS activation in cancer cells, including A549 and U118 cells. To confirm this phenomenon, in this study, we treated both A549 and U118 cells with 2OHOA and measured SMS activity. To our surprise, we found neither 2OHOA-mediated SMS activation nor sphingomyelin accumulation in the cells. However, we noted that 2OHOA significantly reduces phosphatidylcholine in these cells. We also did not observe 2OHOAmediated SMS activation in mouse tissue homogenates. Importantly, 2OHOA inhibited rather than activated recombinant SMS1 (rSMS1) and rSMS2 in a dose-dependent fashion. Intragastric treatment of C57BL/6J mice with 2OHOA for 10 days had no effects on liver and small intestine SMS activities and plasma sphingomyelin levels. The treatment inhibited lysophosphatidylcholine acyltransferase (LPCAT) activity, consistent with the aforementioned reduction in plasma phosphatidylcholine. Because total cellular phosphatidylcholine is used as a predictive biomarker for monitoring tumor responses, the previously reported 2OHOA-mediated cancer suppression could be related to this phosphatidylcholine reduction, which may influence cell membrane structure and properties. We conclude that 2OHOA is not a SMS activator and that its anticancer property may be related to an effect on phosphatidylcholine metabolism.2-Hydroxy-oleic acid (2OHOA) 3 is a potent anticancer drug that induces cancer cell cycle arrest (1), differentiation (2), and death (3-5). The European Medicines Agency has designated 2OHOA as an orphan drug for the treatment of glioma.However, the underlying mechanisms leading to cancer cell death remain largely unknown, although it has been reported that the effect was mediated by activation of sphingomyelin synthase (SMS) in cancer cells and accumulation of cell sphingomyelin levels (6).The biochemical synthesis of SM occurs through the action ofserinepalmitoyltransferase,3-ketosphinganinereductase,ceramide synthase, dihydroceramide desaturase, and SMS (7). SMS catalyzes the conversion of ceramide to sphingomyelin. The SMS gene family consists of three members, SMS1, SMS2, and SMS-related protein (SMSr). SMS1 is found in the trans-Golgi complex, whereas SMS2 is predominantly found in the plasma membranes (8,9). SMSr, the third member of the gene family, has no SMS activity but catalyzes the synthesis of ceramide-phosphoethanolamine in the ER lumen (8, 10). We and another research group reported that systemic SMS1 KO exhibited moderate neonatal lethality (11, 12) (i.e. 25% of homozygotes die during the first 3 weeks; the remainder can grow to adulthood). On the other hand, SMS2 KO mice display no obvious abnormalities and grow to adulthood (13). We and others have suggested that SMS2 might be a therapeutic target for metabolic diseases, including type 2 diabetes, fatty liver, and atherosclerosis (14 -20). However, ...

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Phospholipid Composition and Electric Charge in Healthy and Cancerous Parts of Human Kidneys

Cited by 37 publications

References 24 publications

Changes in the Physico-Chemical Properties of Human Kidney Cell Membranes during the Cancer Transformation

Changes in the Physico-Chemical Properties of Human Kidney Cell Membranes during the Cancer Transformation

Low C24‐OH and C22‐OH sulfatides in human renal cell carcinoma

2-Hydroxy-oleic acid does not activate sphingomyelin synthase activity

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