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BioMed Research International 2020Multiple myeloma (MM) is a devastating cancer with a highly heterogeneous outcome. Because of the heterogeneity of myeloma cells, risk stratification is important for...
Multiple myeloma (MM) is a devastating cancer with a highly heterogeneous outcome. Because of the heterogeneity of myeloma cells, risk stratification is important for making therapeutic regimens. Nevertheless, no immunohistochemical predictive and prognostic marker has been constructed yet. In the present study, we explored the prognostic value of proteolipid protein 2 (PLP2) in MM patients using immunohistochemistry (IHC). We assessed PLP2 expression in bone marrow (BM) biopsy specimens obtained from 87 newly diagnosed MM (NDMM) patients. Correlations between PLP2 expression and clinicopathological features were analyzed. PLP2 expression was present in high-risk MM patients, which was increased with disease progression and poor prognosis. PLP2 was increasing in parallel with high beta-2 microglobulin (2-MG) and lactate dehydrogenase (LDH). Furthermore, MM patients with low PLP2 expression could achieve a favorable treatment response. PLP2 may be a novel biomarker for prognostic prediction and a therapeutic target for anti-MM treatments.
Topics: Aged; Bone Marrow; Female; Humans; MARVEL Domain-Containing Proteins; Male; Middle Aged; Multiple Myeloma; Prognosis; Proteolipids
PubMed: 32596309
DOI: 10.1155/2020/4286101 -
Methods in Molecular Biology (Clifton,... 2018Measuring transport activity through reconstituted proteoliposomes is a key technique to resolve numerous problems found in the traditional methods. The system includes...
Measuring transport activity through reconstituted proteoliposomes is a key technique to resolve numerous problems found in the traditional methods. The system includes overexpression, purification, and reconstitution of transporters. Mixing of purified transporter with lipid and dilution below the critical micelle concentration result in rapid generation of proteoliposomes. Incubation of proteoliposomes in the presence of a driving force initiates substrate uptake. After starting the reaction, samples are passed through a gel filtration column to separate proteoliposomes from the reaction mixture. Here, we describe step-by-step procedures for such reconstitution assays.
Topics: Animals; Chromatography, Gel; Eukaryota; Genomics; Hydrogen; Kinetics; Liposomes; Membrane Transport Proteins; Mice; Proteolipids; Sodium; Substrate Specificity
PubMed: 29177840
DOI: 10.1007/978-1-4939-7454-2_19 -
American Journal of Physiology.... Feb 2023Proteolipid protein 1 (Plp1) is highly expressed in enteric glia, labeling cells throughout the mucosa, muscularis, and the extrinsic innervation. Plp1 is a major...
Proteolipid protein 1 (Plp1) is highly expressed in enteric glia, labeling cells throughout the mucosa, muscularis, and the extrinsic innervation. Plp1 is a major constituent of myelin in the central and peripheral nervous systems, but the absence of myelin in the enteric nervous system (ENS) suggests another role for Plp1 in the gut. Although the functions of enteric glia are still being established, there is strong evidence that they regulate intestinal motility and permeability. To interrogate the role of Plp1 in enteric glia, we investigated gut motility, secretomotor function and permeability, and evaluated the ENS in mice lacking Plp1. We studied two time points: ∼3 mo (young) and >1 yr (old). Old Plp1 null mice exhibited increased fecal output, decreased fecal water content, faster whole gut transit times, reduced intestinal permeability, and faster colonic migrating motor complexes. Interestingly, in both young and old mice, the ENS exhibited normal glial and neuronal numbers as well as glial arborization density in the absence of Plp1. As Plp1-associated functions involve mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (Mapk/Erk1/2) signaling and Mapk/Erk1/2 are reported to have a regulatory role in intestinal motility, we measured protein expression of Erk1/2 and its active form in the small intestine. Old Plp1 null mice had reduced levels of phosphorylated-Erk1/2. Although Plp1 is not required for the normal appearance of enteric glial cells, it has a regulatory role in intestinal motility and barrier function. Our results suggest that functional changes mediated by Plp1-expressing enteric glia may involve Erk1/2 activation. Here, we describe that Plp1 regulates gut motility and barrier function. The functional effects of Plp1 eradication are only seen in old mice, not young. The effects of Plp1 appear to be mediated through the Erk1/2 pathway.
Topics: Animals; Mice; Enteric Nervous System; Gastrointestinal Motility; Mice, Knockout; Neuroglia; Neurons; Proteolipids; Myelin Proteolipid Protein; Intestinal Mucosa
PubMed: 36511517
DOI: 10.1152/ajpgi.00171.2022 -
Annals of the New York Academy of... 2000Secretory lipophilins are "lipid-loving" proteins that are major constituents of several mammalian secretions, including the prostatic fluid of rats and the tears of...
Secretory lipophilins are "lipid-loving" proteins that are major constituents of several mammalian secretions, including the prostatic fluid of rats and the tears of humans and rabbits. These proteins form covalent heterodimers that are stabilized by three intramolecular cystine disulfide bonds. The heterodimers, some of which are glycosylated, may undergo additional non-covalent assembly to form tetramers. The peptide components found in secretory lipophilins are from two subfamilies: lipophilins A/B and lipophilin C. The C subfamily members described in this report are three rabbit and one human lipophilin, plus human mammaglobin and the C3 subunit of rat prostatein. Human A/B and C lipophilins are expressed by many tissues and are especially prominent in endocrine-responsive organs. The gene for human lipophilin B resides at chromosome 10q22-23. This region harbors the PTEN/MMAC1 gene and is believed to contain additional tumor suppressor genes. Although the functions of secretory lipophilins are imperfectly understood, their abundance in glandular secretions and in hormone-responsive tissues suggests that they deserve considerably more attention than they have received to date.
Topics: Animals; Bodily Secretions; Chromatography, High Pressure Liquid; Humans; Mammaglobin B; Myelin Proteins; Phylogeny; Proteolipids; Secretoglobins; Sequence Homology, Amino Acid; Tears; Uteroglobin
PubMed: 11193779
DOI: 10.1111/j.1749-6632.2000.tb05519.x -
FEBS Letters Dec 1995VIP17 is a proteolipid enriched in the CHAPS-insoluble complexes from MDCK cells, and a candidate component of the molecular machinery responsible for the sorting and...
VIP17 is a proteolipid enriched in the CHAPS-insoluble complexes from MDCK cells, and a candidate component of the molecular machinery responsible for the sorting and targeting of proteins to the apical surface. Cloning and sequencing of the cDNA encoding the protein revealed that it is the canine homolog of the human and rat MAL proteins. Analysis by immunofluorescence microscopy of epitope-tagged VIP17/MAL expressed transiently in BHK cells and stably in MDCK cells revealed a perinuclear, vesicular, and plasmalemmal staining. In MDCK cells the distribution was mainly in vesicular structures in the apical cytoplasm. These and other results suggest that VIP17/MAL is an important component in vesicular trafficking cycling between the Golgi complex and the apical plasma membrane.
Topics: Amino Acid Sequence; Animals; Base Sequence; Biological Transport; Cell Compartmentation; Cell Polarity; Cloning, Molecular; DNA, Complementary; Dogs; Fluorescent Antibody Technique; Kidney; Membrane Transport Proteins; Molecular Sequence Data; Myelin Proteins; Myelin and Lymphocyte-Associated Proteolipid Proteins; Proteolipids; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Transfection
PubMed: 8549777
DOI: 10.1016/0014-5793(95)01396-2 -
Vaccine Apr 1989Worldwide, influenza virus remains a serious disease which has successfully eluded numerous attempts to design a consistently effective vaccine. In part, these attempts...
Worldwide, influenza virus remains a serious disease which has successfully eluded numerous attempts to design a consistently effective vaccine. In part, these attempts have been thwarted because of a lack of basic understanding of the mechanisms which mediate protection and recovery from influenza infection. A better understanding of the roles of secretory antibody, serum antibody and cell mediated immunity vis-à-vis protection and recovery from influenza infection has allowed us more rationally to approach the design and administration of a vaccine for influenza. We have constructed a vaccine composed of glycoproteins from the envelopes of either influenza of Sendai virus embedded in a lipid bilayer (immunosomes) mimicking the presentation of the virus to the cells during natural infection. Intranasal immunization with these immunosomes induces an adequate systemic Ir compared with intramuscular immunization and a superior local IgA response. These animals were specifically protected from virus challenge.
Topics: Administration, Intranasal; Animals; Chick Embryo; Immunization; Influenza Vaccines; Lung Diseases; Mice; Nose Diseases; Orthomyxoviridae Infections; Parainfluenza Virus 1, Human; Paramyxoviridae Infections; Proteolipids
PubMed: 2546328
DOI: 10.1016/0264-410x(89)90055-8 -
Molecular Biology of the Cell Nov 2010The renal-specific Na+-K+-2Cl- cotransporter (NKCC2) is the major salt transport pathway of the apical membrane of the mammalian thick ascending limb of Henle's loop....
The renal-specific Na+-K+-2Cl- cotransporter (NKCC2) is the major salt transport pathway of the apical membrane of the mammalian thick ascending limb of Henle's loop. Here, we analyze the role of the tetraspan protein myelin and lymphocytes-associated protein (MAL)/VIP17 in the regulation of NKCC2. We demonstrated that 1) NKCC2 and MAL/VIP17 colocalize and coimmunoprecipitate in Lilly Laboratories cell porcine kidney cells (LLC-PK1) as well as in rat kidney medullae, 2) a 150-amino acid stretch of NKCC2 C-terminal tail is involved in the interaction with MAL/VIP17, 3) MAL/VIP17 increases the cell surface retention of NKCC2 by attenuating its internalization, and 4) this coincides with an increase in cotransporter phosphorylation. Interestingly, overexpression of MAL/VIP17 in the kidney of transgenic mice results in cysts formation in distal nephron structures consistent with the hypothesis that MAL/VIP17 plays an important role in apical sorting or in maintaining the stability of the apical membrane. The NKCC2 expressed in these mice was highly glycosylated and phosphorylated, suggesting that MAL/VIP17 also is involved in the stabilization of NKCC2 at the apical membrane in vivo. Thus, the involvement of MAL/VIP17 in the activation and surface expression of NKCC2 could play an important role in the regulated absorption of Na+ and Cl- in the kidney.
Topics: Animals; Blotting, Western; Cell Line; Endocytosis; Epithelial Cells; Humans; Immunoprecipitation; Kidney; LLC-PK1 Cells; Membrane Transport Proteins; Mice; Mice, Transgenic; Myelin Proteins; Myelin and Lymphocyte-Associated Proteolipid Proteins; Phosphorylation; Protein Binding; Proteolipids; RNA Interference; Rats; Rats, Inbred WKY; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 1; Swine
PubMed: 20861303
DOI: 10.1091/mbc.E10-05-0456 -
Journal of Physiology and Biochemistry Nov 2017Sarcolipin is a transmembrane protein expressed in the sarco/endoplasmic reticulum of skeletal and atrial muscles in large animals. Sarcolipin plays crucial roles in...
Sarcolipin is a transmembrane protein expressed in the sarco/endoplasmic reticulum of skeletal and atrial muscles in large animals. Sarcolipin plays crucial roles in heat production through modifying the function of sarco/endoplasmic reticulum Ca ATPase, thereby being involved in thermogenesis and systemic metabolism. In skeletal muscle, endoplasmic reticulum (ER) stress has been implicated in several conditions, such as insulin resistance, muscle diseases, and hypo/hyper-contraction. Here, we investigated the effect of ER stress on sarcolipin expression in skeletal muscle cells, C2C12 myotubes. First, gene expression of sarcolipin was confirmed in the cells during myogenesis. Then, ER stress was induced in C2C12 myotubes by treatment with tunicamycin or thapsigargin. Sarcolipin messenger RNA (mRNA) and protein expression were significantly reduced by ER stress induction. The reduction was independent of inositol-requiring element 1 (IRE1), which is activated by ER stress and has potent endonuclease activity, when evaluated by treatment with an IRE1 inhibitor, 4μ8C. On the other hand, sarcolipin mRNA stability was reduced under the ER stress when evaluated by treatment with actinomycin D. In conclusion, these results show that ER stress represses sarcolipin expression due to changes in mRNA stability in C2C12 myotubes.
Topics: Animals; Cell Line; Endoplasmic Reticulum Stress; Gene Expression; Mice; Muscle Fibers, Skeletal; Muscle Proteins; Proteolipids
PubMed: 28707279
DOI: 10.1007/s13105-017-0578-9 -
Journal of Virology Jan 2020Myelin and lymphocyte protein (MAL) is a tetraspan integral membrane protein that resides in detergent-insoluble membrane fractions enriched in condensed membranes. MAL...
Myelin and lymphocyte protein (MAL) is a tetraspan integral membrane protein that resides in detergent-insoluble membrane fractions enriched in condensed membranes. MAL is expressed in oligodendrocytes, in Schwann cells, where it is essential for the stability of myelin, and at the apical membrane of epithelial cells, where it has a critical role in transport. In T lymphocytes, MAL is found at the immunological synapse and plays a crucial role in exosome secretion. However, no involvement of MAL in viral infections has been reported so far. Here, we show that herpes simplex virus 1 (HSV-1) virions travel in association with MAL-positive structures to reach the end of cellular processes, which contact uninfected oligodendrocytes. Importantly, the depletion of MAL led to a significant decrease in infection, with a drastic reduction in the number of lytic plaques in MAL-silenced cells. These results suggest a significant role for MAL in viral spread at cell contacts. The participation of MAL in the cell-to-cell spread of HSV-1 may shed light on the involvement of proteolipids in this process. Herpes simplex virus 1 (HSV-1) is a neurotropic pathogen that can infect many types of cells and establish latent infections in neurons. HSV-1 may spread from infected to uninfected cells by two main routes: by cell-free virus or by cell-to-cell spread. In the first case, virions exit into the extracellular space and then infect another cell from the outside. In the second case, viral transmission occurs through cell-to-cell contacts via a mechanism that is still poorly understood. A third mode of spread, using extracellular vesicles, also exists. In this study, we demonstrate the important role for a myelin protein, myelin and lymphocyte protein (MAL), in the process of cell-to-cell viral spread in oligodendrocytes. We show that MAL is involved in trafficking of virions along cell processes and that MAL depletion produces a significant alteration in the viral cycle, which reduces cell-to cell spread of HSV-1.
Topics: Cell Line, Tumor; Cell Membrane; Epithelial Cells; Herpes Simplex; Herpesvirus 1, Human; Humans; Lymphocytes; Membrane Proteins; Myelin Proteins; Myelin and Lymphocyte-Associated Proteolipid Proteins; Neurons; Oligodendroglia; Proteolipids; T-Lymphocytes
PubMed: 31748392
DOI: 10.1128/JVI.01739-19 -
The Journal of Biological Chemistry Nov 1987Two newly described surfactant proteolipids (SPL), Phe and pVal, are produced by proteolytic processing of distinct precursors of Mr = 40,000 and 22,000, respectively....
Two newly described surfactant proteolipids (SPL), Phe and pVal, are produced by proteolytic processing of distinct precursors of Mr = 40,000 and 22,000, respectively. These proteins are structurally related and intimately associated with surfactant phospholipids. We now demonstrate the expression of both SPL(Phe) and SPL(pVal) in explants of human fetal lung from 16-24 weeks of gestation. Content, synthesis, and mRNA for the proteolipids were low prior to organ culture of fetal lung. Induction of synthesis of the proteolipids occurred rapidly in explant culture in the absence of exogenous hormones and was enhanced by addition of dexamethasone. Increased synthesis of the proteolipids was detected by enzyme-linked immunosorbent assay and by [35S]methionine incorporation into the glycosylated Mr = 40,000-43,000 SPL (Phe) precursor. The response to dexamethasone occurred rapidly and contrasted with effects of dexamethasone on the expression of surfactant-associated protein- (SAP) 35, a distinct surfactant glycoprotein. 8-Br-cAMP did not significantly increase proteolipid content but markedly increased synthesis of SAP-35 in identical cultures. Increased proteolipid content was associated with increased mRNA for each protein as determined by the Northern blot analysis. Proteolipid RNA was also increased by 8-Br-cAMP, however, not to the extent observed with the glucocorticoid. Immunohistochemical analysis of fetal lung with anti-proteolipid antiserum confirmed that the dexamethasone-enhanced synthesis of the proteins by Type II epithelial cells. The time and hormone dependence of the regulation of expression of both SPL(Phe) and SPL(pVal) precursors were distinct from that of SAP-35. Expression of the surfactant proteolipids increased during explant culture of human fetal lung and was further enhanced by glucocorticoid. Developmental and hormonal regulation of the surfactant proteolipids may be important factors in surfactant function at birth.
Topics: Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Glucocorticoids; Humans; Immunohistochemistry; Lung; Methionine; Molecular Weight; Peptides; Proteolipids; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein C; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; RNA
PubMed: 2445738
DOI: No ID Found