Membrane Lipid Replacement: Clinical Studies Using a Natural Medicine Approach to Restoring Membrane Function and Improving Health

Functional oral supplements containing cell membrane glycerolphospholipids and antioxidants have been used to safely replace damaged membrane lipids that accumulate during aging and in various clinical conditions. This approach differs from other dietary and intravenous interventions in the composition of phospholipids and the presence of fructooligosaccharides that protect the phospholipids against oxidation and bile and enzymatic damage. Various chronic clinical conditions are characterized by membrane phospholipid oxidative damage, resulting in loss of cellular function. Recent clinical trials have shown the benefits of Membrane Lipid Replacement in replenishing damaged membrane lipids and restoring mitochondrial function, resulting in reductions in fatigue in aged subjects and patients with a variety of clinical diagnoses. Recent in vitro experiments with nonphysiological concentrations of phospholipids did not result in enhancement of mitochondrial electron transport enzyme activities. This can be explained by the use of the wrong phospholipid fatty acids, over-dilution of membrane constituents and mitochondrial swelling. A similar phenomenon was seen when human sperm were incubated in vitro with high concentrations of glycerolphospholipids and their motility was assessed. Only lower, more physiological concentrations of glycerolphospholipids stimulated sperm motility. Additional studies are needed to determine the functional effects of Membrane Lipid Replacement on other cellular membranes, such as the plasma membrane and other intracellular membranes of various cells and tissues.

Effects of cell membrane phospholipid level and protein kinase C isoenzyme expression on hepatic metastasis of colorectal carcinoma

BACKGROUND: The molecular mechanism of hepaticmetastasis of colorectal cancer is not well understood. Theaim of this study was to assess the relations between phos-pholipid contents of cellular membrane and isoenzyme ex-pression of protein kinase C (PKC) and their effects on he-patic metastasis of colorectal cancer.METHODS: High performance liquid chromatography wasused to detect contents of cell membrane phospholipids:phosphatidylinosital (PI), phosphatidylserine (PS), phos-phatidylethanolamine (PE) and phosphatidylcholine (PC)in primary foci, paratumor mucosa and hepatic metastaticfoci in patients with colorectal carcinoma. The mRNA ex-pression levels of PKC-α, -δ, -ε, -λ, -ξ isoenzymeswere detected with the QRT-PCR technique.RESULTS: The levels of PI, PC and PE in primary foci andhepatic metastatic foci were higher than those in paratumormucosa. The level of PE in hepatic metastatic foci wasmuch higher than that in primary foci (t =98.88, P <0.01);but the levels of PI and PC were not significantly differentbetween primary foci and hepatic metastatic foci (t =1.73 ,1.36, P>0.05). The expression levels of -δ, -ε,-λ, -ξ were enhanced in primary foci and hepatic metasta-tic foci, but the level of PKC-α in primary foci was de-creased as compared with that in paratumor mucosa. Thelevels of PKC-δ, -ε, -λ, -ξ in hepatic metastatic foci werehigher than those in primary foci. A positive correlationwas observed between the expression levels of PI, PC andand also between those of PE and PKC-δ, -ε, -λ,-ξ. However, there was a close negative correlation be-tween PE and PKC-α.CONCLUSION: Increased levels of PI and PC and de-creased ratio of PKC-α to are related to colorectalcancer genesis. Increased levels of PE, increased expressionof PKC-δ, -ε, -λ, -ξ isoenzymes and decreased level ofPKC-α are related to hepatic metastasis in colorectal carci-noma.

Formation mechanism for stable system of nanoparticle/protein corona and phospholipid membrane

In the physiological environment, nanoparticles(NPs) interact with proteins to form a protein-rich layer on the surface which is called "protein corona". Understanding and analyzing the formation process of protein corona and protein corona-nanoparticles is of great significance for biological related nano research. Many separation techniques have been used to analyze the composition of protein corona, but in situ analysis of protein corona is still absent. With the development of detection technology, sum frequency generation(SFG) is an effective instrument to analyze the surface protein structure and dynamic changes of protein corona in situ. In this work the molecular mechanism and surface structure effect of the interaction between nanoparticles with surface protein corona(S-NPP) and phospholipid membrane were studied. When S-NPP interacts with phospholipid membrane, the bond affinity network formed by the binding water can stabilize S-NPP around the lipid bilayer. In this process, S-NPP can be found wrapped in the hydration shell. This ultimately leads to a more moderate interaction between particles and phospholipid membrane.

Impairment of Myocardial and Skeletal Mitochondria in Mice with Viral Myocarditis and Their Correlation

In order to investigate the impairment of mitochondrial membrane phospholipid local- ization and DNA3867 (mtDNA3867) deletion and the correlation between cardiac and skeletal muscle cells in mice with viral myocarditis, 50 BALB/c mice were divided into two groups randomly. In ex- perimental group (n=40), the mice were intraperitoneally injected with 0.1 mL Eagle liquid with CVB3 (TCID50=108), while in the control group (n=10), the mice were subjected to equal volume of Eagle liquid. The impairment of mitochondrial membrane phospholipid localization and mtDNA3867 deletion rate of cardiac and skeletal muscle were detected separately at day 3, 11 and 24 after injec- tion. The correlation of mitochondrial membrane phospholipid localization and mtDNA3867 deletion rate between cardiac and skeletal muscle cells cells was analyzed using Spearman method. At the day 3 after injection, in both cardiac and skeletal muscle cells, mtDNA3867 deletion rate was significantly higher in experimental group than in control group (P<0.05), but the localization of mitochondrial membrane phospholipid showed no difference between two groups (P>0.05). At day 11 after injec- tion, the mtDNA3867 deletion rate of both cells in experimental group was increased to the peak level (P<0.05), and the impairment of mitochondrial membrane phospholipid localization of both cells also increased markedly in experimental group as compared with control group (P>0.05). At the day 24 after injection, the impairment of mitochondrial membrane phospholipid localization and mtDNA3867 deletion of both cells showed a recovery tendency, but still severer than those at the day 3 after injec- tion (P<0.05). The impairment of mitochondrial membrane phospholipid localization and mtDNA3867 deletion were consistent and synchronistic between cardiac and skeletal muscle cells, and showed good correlations (P<0.05). The impairment of mitochondria plays an important role in the patho- genesis of viral myocarditis, and the skeletal muscle cells might act as a peripheral 'window' to re- flect the mitochondrial damage of cardiac myocytes.

Membrane-bound O-acyltransferases(MBOATs)

The MBOATenzyme family,identified in 2000,comprises 11 genes in the human genome that participate in a variety of biological processes.MBOAT enzymes contain multiple transmembrane domains and share two active site residues,histidine and asparagine.Several MBOAT members are drug targets for major human diseases,including atherosclerosis,obesity,Alzheimer disease,and viral infections.Here we review the historical aspects of MBOAT enzymes,classify them biochemically into 3 subgroups,and describe the essential features of each member.