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Comparative Anatomy, Physiology, and Biochemistry of Mammalian Skin
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
The plasma cell is usually found in loose connective tissue and in great numbers in lymphatic tissue. It is derived from B-lymphocytes which differentiate in the connective tissue after antigenic stimulation. Antibody production is the function of the plasma cell (see Chapter 5). In routine staining for light microscopy, plasma cells can be seen to contain a large amount of cytoplasm relative to the size of the nucleus. The nuclear chromatin is distributed in clumps around the periphery of the cell. The nucleolus is prominent. The plasma cell can sometimes contain acidophilic granules termed Russel bodies. Ultrastructurally, plasma cells have an abundance of rough endoplasmic reticulum and prominent organelles such as a large Golgi region, mitochondria, polyribosomes, and finger-like extensions of the plasma membrane. The abundance of rough endoplasmic reticulum suggests protein secretion, a finding consist with their role of producing antibodies for release into the blood.204
Airway Wall Remodelling in the Pathogenesis of Asthma: Cytokine Expression in the Airways
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
Peter Bradding, Anthony E. Redington, Stephen T. Holgate
Many studies have approached the investigation of cytokine expression in the airways by studying mRNA for the molecule of interest using such techniques as Northern blot analysis, in situ hybridisation, and most recently the reverse transcriptase polymerase chain reaction (RT-PCR). However, when interpreting such studies it must be remembered that the presence of mRNA does not necessarily imply that there is translation into protein,14 let alone protein secretion. An alternative approach has been to investigate the expression of cytokine protein using immunohistochemistry. However, the presence of immunoreactive cytokine protein within the airways may not provide an accurate reflection of its release. It is probably too simplistic to assume that quantification of numbers of cytokine-expressing cells in a tissue can provide an accurate guide to cytokine activity in a disease setting.
Intracellular Maturation of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Erik Fries, E. Mathilda Sjöberg
In 1984, Hille et al.78 reported that after the injection of [35S]sulfate into rats, labeled proteins could be detected in all tissues investigated, including blood plasma. Further analysis showed that the sulfate groups on proteins in tissues other than blood were linked mainly to carbohydrates, whereas those in plasma were linked mainly to tyrosine residues. Based on this and the earlier observation that certain secretory proteins contain sulfated tyrosines, they proposed that sulfate residues might have a function in protein secretion. However, reagents that could inhibit this modification showed that tyrosine sulfation was irrelevant to secretion.79 Tyrosine sulfation has been shown to take place in the trans-Golgi, apparently after sialylation.80,81
Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis
Published in OncoImmunology, 2020
Oliver Kepp, Peng Liu, Liwei Zhao, Isabelle Plo, Guido Kroemer
Exon 9 mutations of CALR have been identified in up to 30% of patients affected by myeloproliferative neoplasms (MPNs) such as essential thrombocythemia (ET) and myelofibrosis (MF).33,34 The most recurrent mutations typically manifest as either a 52 base pair deletion of residues 1092 to 1142 (CALRdel52) or a 5 base pair insertion between residues 1154 and 1155 (CALRins5). Both mutations lead to an alternative open reading frame, resulting in similar changes in the C-terminal amino acid sequence of the protein that becomes positively charged and loses the KDEL ER retention signal.35 Consequently, mutant CALR protein fails to be detected by KDEL retention receptors and thus enters the conventional protein secretion pathway and is released via Golgi-mediated exocytosis.30,36,37 Secreted CALR mutants bind (via their lectin binding sites) to the extracellular domain of the thrombopoietin receptor (MPL) in a cell autonomously or paracrine fashion thus leading to a downstream activation of the Janus kinase 2 (JAK2) and signal transducer and activator of transcription (STAT) proteins STAT1, STAT3 and STAT5.38-41 Introduction of analogous CALR mutations into mice recapitulates the ET-like disease and its progression to myelofibrosis.41-43 Thus, CALR mutants act as oncogenic driver of MPN.39,41,44,45 Moreover, patients with MPN-associated CALR mutations exhibit an increase in myeloid derived suppressor cells (MDSC) and immunosuppressive B cells, suggesting that mutated CALR may subvert immune responses.44,46
The secrets of protein secretion: what are the key features of comparative secretomics?
Published in Expert Review of Proteomics, 2020
How proteins are selected and secreted from the crowded intracellular space is a key question in biology [1]. Besides the classical ER-Golgi exocytic route, which still dominates the detailed characterization of secretomes (all proteins secreted by a cell), three additional unconventional secretory pathways have been described: (i) Golgi-bypassing of membrane proteins, (ii) pore-mediated secretion (lipid or proteinaceous pore), and (iii) vesicle-mediated secretion (secretory lysosomes, endosomes and multivesicular bodies) [1,2]. The main reasons for the dominance of classical secretion for the full characterization of secretomes are, besides its partially higher protein abundance, (i) the concept of classical secretion relies on a well-established signal hypothesis is [3], (ii) classically secreted proteins can be predicted due to their N-terminal signal peptide and thereby differentiated from intracellular ‘contaminants’ [4], and (iii) analytical tools (e.g. specific secretion inhibitors brefeldin A and monensin) are available that allow validation of the classical secretory pathway. However, a growing body of experimental data shows that a large proportion of secreted proteins are released by unconventional secretory pathways and are not intracellular contaminants, as considered previously. Particularly, data from proteomic studies contribute to this observation [5]. In contrast to classical protein secretion, for proteins released by unconventional secretory pathways, a signal motif has not yet been described, and analytical tools that allow identification of the underlying secretory pathways remain scarce. Due to these factors, full characterization of the ‘unconventional secretome’ has not yet been realized. Thus, alternative approaches have been developed and applied to unravel these mechanisms of protein secretion. In this context, comparative secretomics has proven to be a versatile tool to allow full characterization of the secretome [6].
Bifidobacterium animalis: the missing link for the cancer-preventive effect of Gynostemma pentaphyllum
Published in Gut Microbes, 2021
Weilin Liao, Imran Khan, Guoxin Huang, Shengshuang Chen, Liang Liu, Wai Kit Leong, Xiao Ang Li, Jianlin Wu, W. L. Wendy Hsiao
To further investigate whether GpS treatment could alter the biosynthesis and metabolism of the bacteria, we looked into the transcriptome of B. animalis in the presence and absence of GpS using RNAseq analysis. By comparing to the Ctrl, we identified 25 genes uniquely expressed in the GpS-treated culture of B. animalis. These genes are mapped to various biosynthesis pathways using the KEGG Mapper (Figure 5b). For instance, on the map, hisB, hisH, and hisI are part of the 10-gene cluster encode steps in the histidine biosynthetic pathway.34ArgJ encodes duel enzymes for arginine biosynthesis. MetF encodes 5,10-methylenetetrahydrofolate reductase, responsible for converting dUMP to dTMP for de novo synthesis. PyrB is mapped to pyrimidine biosynthesis; and miaA, tadA, tsaB, ybeY encode enzymes for RNA editing and synthesis.35 Besides playing the roles in biogenesis and biosynthesis as described above, some of the genes have different unique functions; for instance, recR encodes RecR protein, together with RecF and RecO proteins, forms the RecFOR complex which functions in RecA-mediated replication and homologous recombination. The recA, F, and O genes are all upregulated in GpS-cultures (Figure 5c). Another interesting gene, ruvA, encores part of RuvA-B DNA helicase for DNA repair and recombination.36 RuvB is also found upregulated on our gene list (Figure 5c and Table S2). Both the RuvA-B complex and the RecR are critical to bacterial DNA repair. The yajC gene encodes the smaller subunit of the preprotein translocase complex, which interacts with membrane protein SecD and SecF to coordinate protein transport and secretion across the cytoplasmic membrane in Escherichia coli.37PstA encodes the subunit of the ABC transporter, and the gatC gene encodes a translation factor. The coaD encodes phosphopantetheine adenyltransferase, which is involved in coenzyme-A biosynthesis. The coaD gene is also a frequent target for antibacterial drug discovery.38 The 4.5 RNA encoded by the ffs gene is the RNA component of the signal recognition particle (SRP) ribonucleoprotein complex that binds to the ribosome. SRP complex involves co-translational protein secretion and requires for cell viability. Deficiency of the gene causes a dramatic loss in protein synthesis, and eventual cell death.39 The rpmH encodes ribosomal 50S ribosomal subunit protein L34. It is worth mentioning that good numbers of upregulated genes in GpS-culture are the genes encoding 50S and 30S ribosomal subunit proteins (Figure 5c and Table S2). Transcription of rRNA is an essential step in ribosome biogenesis, which is highly regulated by the external supply of nutrients or external stimuli. In our case, GpS is well served as the growth stimulus to B. animalis through the activations of a series of genes encoding for rRNA and various biogenesis protein molecules, as illustrated above.