Cell-penetrating peptides (CPPs) are short peptides that can penetrate the cell membrane or tissue barrier. CPPs can deliver a variety of biomacromolecules, such as proteins, RNA and DNA, into cells to produce intracellular functional effects. Endocytosis and direct penetration have been suggested as the two major uptake mechanisms for CPPs-mediated cargo delivery. Compared with other non-natural chemical molecules-based delivery reagents, the CPPs have better biocompatibility, lower cytotoxicity, are easily degraded after cargo delivery, and can be fused and recombined expressed with bioactive proteins. Because of these advantages, the CPPs have become an important potential tool for delivery of developing drugs which targets intracellular factors. As a novel delivery tool, the CPPs also show promising application prospects in biomedical researches. This review summarized recent advances regarding the classification characteristics, the cellular uptake mechanisms and therapeutic application potentials of CPPs.
Biological Transport ; Cell Membrane ; Cell-Penetrating Peptides ; metabolism ; Endocytosis

Glycosphingolipids (GSLs) are widely distributed in the phospholipid bilayer of various cell membranes, which play an important role in maintaining cell membrane stability, and regulate various cellular processes including adhesion, proliferation, apoptosis and recognition, as well as participate in various cellular activities. In addition, GSLs are not only involved in the process of apoptosis, but also regulate multiple signals in tumorigenesis and tumor development. The tumor-associated GSLs are expected to be used as diagnostic markers and immunotherapeutic targets for malignant tumors. These findings have important implications for the study of apoptosis and provide the new direction of tumor therapy. This review summarized the latest research progress of GSLs-mediated apoptosis and its effect on the genesis, development and metastasis of tumor cells. Moreover, we discussed the metabolic pathway of GSLs-mediated apoptosis and its application in tumor therapy, as well as the development prospect of targeted therapy strategies based on GSLs.
Humans ; Glycosphingolipids/metabolism* ; Apoptosis ; Cell Membrane ; Neoplasms/metabolism*

A specialized tissue type, the keratinizing epithelium, protects terrestrial mammals from water loss and noxious physical, chemical and mechanical insults. This barrier between the body and the environment is constantly maintained by reproduction of inner living epidermal keratinocytes which undergo a process of terminal differentiation and then migrate to the surface as interlocking layers of dead stratum corneum cells. These cells provide the bulwark of mechanical and chemical protection, and together with their intercellular lipid surroundings, confer water-impermeability. Much of this barrier function is provided by the cornified cell envelope (CE), an extremely tough protein/lipid polymer structure formed just below the cytoplasmic membrane and subsequently resides on the exterior of the dead cornified cells. It consists of two parts: a protein envelope and a lipid envelope. The protein envelope is thought to contribute to the biomechanical properties of the CE as a result of cross-linking of specialized CE structural proteins by both disulfide bonds and N(epsilon)-(gamma-glutamyl)lysine isopeptide bonds formed by transglutaminases. Some of the structural proteins involved include involucrin, loricrin, small proline rich proteins, keratin intermediate filaments, elafin, cystatin A, and desmosomal proteins. The lipid envelope is located on the exterior of and covalently attached by ester bonds to the protein envelope and consists of a monomolecular layer of omega-hydroxyceramides. These not only serve of provide a Teflon-like coating to the cell, but also interdigitate with the intercellular lipid lamellae perhaps in a Velcro-like fashion. In fact the CE is a common feature of all stratified squamous epithelia, although its precise composition, structure and barrier function requirements vary widely between epithelia. Recent work has shown that a number of diseases which display defective epidermal barrier function, generically known as ichthyoses, are the result of genetic defects of the synthesis of either CE proteins, the transglutaminase 1 cross-linking enzyme, or defective metabolism of skin lipids.
Animal ; Cell Membrane/metabolism ; Epidermis/metabolism* ; Epidermis/chemistry* ; Human ; Ichthyosis/metabolism ; Ichthyosis/genetics ; Keratinocytes/metabolism* ; Keratinocytes/chemistry ; Membrane Lipids/metabolism* ; Membrane Proteins/metabolism* ; Protein-Glutamine gamma-Glutamyltransferase/metabolism

Animals ; Cell Membrane ; chemistry ; metabolism ; Humans ; Membrane Proteins ; chemistry ; metabolism ; Protein Structure, Secondary

OBJECTIVETo explore whether the membrane-associated protein Flotillin-1 has relationship with endocytosis of PrPc.

METHODSThe expression of Flotillin-1 in different cell lines was detected with the method of Western Blot; the interaction between Flotillin-1 and PrPc in Cells which were treated with copper ions was observed using immunoprecipitation method.

RESULTS(1) Flotillin-1 was widely expressed in many cell lines without significant difference in the amounts of expression level; (2) Only in the appearance of copper ions, the protein complexes of PrPc and Flotillin-1 can be detected with the method of IP, which were related to copper ions concentration and processing time.

CONCLUSIONThe membrane-associated protein Flotillin-1 has the relationship with the endocytosis of PrPc.

Cell Line ; Cell Membrane ; genetics ; metabolism ; Endocytosis ; Humans ; Membrane Proteins ; genetics ; metabolism ; PrPC Proteins ; genetics ; metabolism ; Protein Binding ; Protein Transport

OBJECTIVETo investigate the expression of cell surface E-cadherin in leukemia cell and the correlation of cell membrane localization of beta-catenin with E-cadherin expression.

METHODSBone marrow samples from 46 patients with acute leukemia and 17 normal donors were analyzed. Cell surface expression of E-cadherin and membrane localization of beta-catenin were labeled by immunofluorescence and analyzed with a laser scanning confocal fluorescence microscope in 14 specimens.

RESULTSCell surface E-cadherin expression level was significantly lower in leukemia cells (with the median fluorescent intensity of 16.78) than in normal hematopoietic progenitors (26.03). Correlation analysis showed that cell membrane localization of beta-catenin was correlated with E-cadherin expression (r = 0.74, P = 0.002). After E-cadherin was induced to express in leukemic cell by 5-Aza-CdR, membranous expression of beta-catenin was elevated while the nuclear expression reduced, indicating that E-cadherin-mediated adhesions could recruit beta-catenin to cell membrane.

CONCLUSIONThe loss of E-cadherin in leukemia cells may result in beta-catenin translocating to the nuclear and transcriptional activation of its target genes.

Cadherins ; metabolism ; Case-Control Studies ; Cell Membrane ; metabolism ; Humans ; Leukemia ; metabolism ; pathology ; beta Catenin ; metabolism

Aquaporin-9 (AQP9) is a membrane-span transport protein expressed in the liver. It is located in the cytoplasm membrane of hepatic cells. In addition to water, it is also permeable to glycerol, urea, and other small solutes. Several evidences have revealed that AQP9 is involved in multiple physiological and pathological process of the liver. This paper summarized the expression of AQP9 in the liver and the effect on the physiological and pathological processes of the liver. AQP9 may be defined as a novel target for diagnosis and treatment of hepatic diseases.
Aquaporins ; metabolism ; Cell Membrane ; metabolism ; Glycerol ; Hepatocytes ; metabolism ; Humans ; Liver ; metabolism ; Urea

Sexual reproduction is marked by the fusion of the sperm cell with the oocyte during fertilization to produce the diploid zygote, in which the lipids in the sperm plasma membrane play an important role. Due to the loss of most cell organelles and DNA transcription, spermatozoa lack protein expression and vesicular transport. However, the lipids of the sperm plasma membrane undergo complicated dynamic changes, which may facilitate the capacitation, binding with zona pellucida, acrosome reaction and fusion of the sperm cell with the oocyte. This paper summarizes the progress in the studies of the lipids in the sperm plasma membrane, their composition, structure, peroxidation, metabolism and role in fertilization.
Acrosome Reaction ; Animals ; Cell Membrane ; chemistry ; Fertilization ; Humans ; Male ; Membrane Lipids ; metabolism ; Sperm Capacitation ; Spermatozoa ; chemistry

PURPOSE: The aim of this study was to determine whether plasma lecithin:cholesterol acyltransferase (pLCAT) and erythrocyte membrane Na(+)-K(+)-ATPase ase (emNaKATPs) activity have a correlation in breast cancer. This study compared these parameters at time points before and after treatment with radiotherapy. METHODS: The levels of pLCAT and emNaKATPs were assessed in 30 patients with breast carcinoma and 20 control subjects. While emNaKATPs was measured with spectrophotometric method, pLCAT levels was measured using a specific enzyme-linked immunosorbent assay. RESULTS: pLCAT levels, both before and after radiotherapy, were found to be decreased in breast cancer patients than in the controls groups (p<0.001 and p<0.001, respectively). Also, pLCAT levels after radiotherapy were found to be decreased in breast cancer patients than the pLCAT levels before radiotherapy (p<0.001). The emNaKATPs activity were higher in the control group than in the breast cancer patients before/after radiotherapy (RT) (p<0.001 and p<0.001, respectively). At the same time, emNaKATPs activity before RT was higher in the breast cancer patients than emNaKATPs activity after RT (p<0.001). There was a significant correlation between pLCAT and emNaKATPs activity in breast cancer patients receiving radiotherapy (r=0.63, p<0.001), but no correlation between in breast cancer patients before RT and control group (r=0.023, p>0.05). CONCLUSION: The results of the present study demonstrated that decreased pLCAT and emNaKATPs activity levels in breast cancer patients after/before RT than control group. In addition, decreased emNaKATPs activity in breast cancer patients receiving radiotherapy may be due to decreased pLCAT concentrations and RT beam. In our opinion, altered activities of pLCAT and emNaKATPs are linked to the treatment effect of radiotherapy. These data may clarify the development of cell membrane dysfunction and lipid metabolism in breast cancer patients receiving radiotherapy.
Breast ; Breast Neoplasms ; Cell Membrane ; Cholesterol ; Erythrocyte Membrane ; Humans ; Lecithins ; Lipid Metabolism ; Plasma ; Sterol O-Acyltransferase

In recent years, many experts have done some researches on experiment and mechanism of intracellular electromanipulation (IEM) under nanosecond pulsed electric field (nsPEF). The experiment results have shown that nsPEF could not induce electroporation of cell membrane, but could induce intracellular effects such as apoptosis, calcium release, enhancement of gene expression, and fragmentation of DNA and chromosome. In order to account for the phenomenon, researchers believe that when the pulse width of the pulsed electric field is larger than the charging time of plasma membrane, the pulsed electric field mainly targets on the outer membrane of cell; and that the effect of the pulsed electric field on nucleus and nuclear membrane increases with the decrease of the pulse width. It is also believed that the effect of electroporation changes from the outer membrane to intracellular electromanipulation when the pulse width decreases to a value being smaller than the charging time of plasma membrane.
Apoptosis ; Calcium ; metabolism ; Cell Membrane ; metabolism ; Cell Nucleus ; metabolism ; Cell Physiological Phenomena ; Electromagnetic Fields ; Electroporation ; Gene Expression