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Lens and cataracts
Published in Mostafa Khalil, Omar Kouli, The Duke Elder Exam of Ophthalmology, 2019
Mannosidosis AR condition due to deficiency in alpha mannosidase.Spoke-shaped posterior cataracts.
Golgi apparatus regulation of differentiation
Published in C. Yan Cheng, Spermatogenesis, 2018
Louis Hermo, Regiana L. Oliveira, Charles E. Smith, Catherine E. Au, John J. M. Bergeron
The Golgi is responsible for glycosylation180 and this occurs during acrosome formation with expression of Man2α1 and ManIIX. These sequence-related proteins likely have related functions in alpha mannosidase trimming of high mannose containing N-linked oligosaccharides.133 The lack of detection of both of these proteins from steps 8–14 would suggest a diminution in Golgi mannosidase activity that in turn would be linked to the well-known major changes in N-linked glycosylation of proteins accounting for the high mannose and complex glycoproteins differentially expressed during spermatogenesis.32,96
Legume Nodule Biochemistry and Function
Published in Peter M. Gresshoff, Molecular Biology of Symbiotic Nitrogen Fixation, 2018
Robert B. Mellor, Dietrich Werner
The peribacteroid space (PBS) is defined as the space between the symbiotic partners. Morphologically it is that space which lies between the outside of the bacteroid and the inside of the peribacteroid membrane. The space is electron-transparent in electron microscopy (EM) but may be isolated and biochemically characterized.16 The PBS contains several proteins which can be separated by SDS-PAGE or urea IEF (isoelectric focusing). Some lytic activities, including a large proportion of proteases, have been reported in the PBS.54 The PBS also contains protease inhibitors55 and it may be on these that effective bacteroids rest in order to escape digestion by the host. The best-characterized protein occurring in the PBS is alpha-mannosidase isoenzyme II. This is found in high concentrations in the PBS and is one of the two vacuolar forms of alpha-mannosidase. The third, isoenzyme III, is found sequestered in the extracellular space.56 Thus, the PBS is in contact with the host cell vacuole and the bacteroid, at least from the point of view of alpha-mannosidase, sits in a lysosome-like environment and not an extracellular environment as was previously thought.
Targeting E7 antigen to the endoplasmic reticulum degradation pathway promotes a potent therapeutic antitumor effect
Published in Journal of Drug Targeting, 2021
David Hernán Martínez-Puente, Rodolfo Garza-Morales, José Juan Pérez-Trujillo, Aracely García-García, Arnulfo Villanueva-Olivo, Humberto Rodríguez-Rocha, Laura Mireya Zavala-Flores, Odila Saucedo-Cárdenas, Roberto Montes de Oca-Luna, María de Jesús Loera-Arias
The accumulation of the misfolded proteins in the ER lumen promotes activation of the ER stress response, leading to the upregulation of chaperone-expression [18]. To evaluate if transfection with the fusion proteins induces an ER stress response, we performed immunofluorescence and western blot analysis of GRP78. Overexpression of GRP78 in those cells transfected with DNA constructs containing E7 (COX2-E7 and COX2-E7ΔERAD) was demonstrated by immunofluorescence, showing a small increase in those cells transfected with COX2-E7ΔERAD. Moreover, GRP78 upregulation comes only from transfected cells, detected by the overlapping of the E7 and GRP78 signals (Figure 3(A)). western blot results show an important overexpression of GRP78, but only in cells transfected with COX2-E7ΔERAD construct (Figure 3(B)). To further validate these results, we performed a real-time PCR analysis. In those cells transfected with COX2-E7 and COX2-E7ΔERAD, we observed a significant increase in RNA expression of GRP78, when compared to the COX-2 construct (p = .0004 and p = .0001, respectively). Interestingly, CHOP expression, which is related to a cell death downstream pathway [19], is not significantly augmented in COX2 and COX2-E7 transfected cells, but we observed significant expression in COX2-E7ΔERAD versus COX2-E7 and COX-2 transfected cells (p = .0051 and p = .0001, respectively). Other downstream proteins, such as activating transcription factor 4 (ATF4) and ER Degradation Enhancing Alpha-Mannosidase Like Protein 1 (EDEM1), were not overexpressed (Figure 3(C)).
Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia
Published in Pharmaceutical Biology, 2021
Zhen-Tao Mo, Jie Zheng, Yu-ling Liao
However, overactivated IRE1α-XBP1 signalling pathway can also induce inflammatory response (Yue et al. 2016). IRE1α is a type I transmembrane protein on ER, which has both kinase and endoribonuclease activities. Under physiological conditions, IRE1α exists in ER as a monomer. When the cells are stimulated by ischaemia and oxidative stress, the ER lumen of unfolded and misfolded proteins accumulates, which stimulates the dimerization of IRE1α, and the carboxyl terminus of IRE1α is subsequently autophosphorylated, thereby activating its kinase and endoribonuclease activities (Concha et al. 2015). Activated IRE1α can phosphorylate and activate its downstream substrate JNK and shear its downstream substrate XBP1 mRNA (Li X et al. 2015; Shi et al. 2018). The unspliced XBP-1 (XBP1u) protein is translated from XBP1mRNA without splicing, while being spliced a 26 BP intron, XBP1u transforms into XBP1s which is an active form of XBP1 and has strong transcriptional activity (Li X et al. 2015). XBP1s, which can enter the nucleus and bind to the X-box in the promoter sequence of unfolded protein response element (UPRE), increase the expression of its target genes such as ER degrading enhancer alpha-mannosidase-like protein (EDEM) and GRP78 which promote the degradation of unfolded proteins, and thus maintains the homeostasis of ER and plays an anti-apoptotic role (Yoshida et al. 2001).
Glycosylation of random IgG distinguishes seropositive and seronegative rheumatoid arthritis
Published in Autoimmunity, 2018
I. Magorivska, B. Döncző, T. Dumych, A. Karmash, M. Boichuk, K. Hychka, M. Mihalj, M. Szabó, E. Csánky, J. Rech, A. Guttman, S. G. Vari, R. Bilyy
The exposure of fucose and of branching GlcNAc is greatly influencing the ADCC of Ab preparation, and thus a main target during the design of efficient monoclonal Ab [25]. It was demonstrated that it is the absence of fucose, not the presence of bisecting N-acetylglucosamine per se, that results in enhanced ADCC [9]. Bisecting N-glycans are formed due to alterations in de novo glycan synthesis, particularly due to the switch from complex to hybrid N-glycan biosynthesis (then enzyme GlcNAcT-III transfers N-acetylglucosamine to the β-linked mannose in the core to generate the bisecting N-acetylglucosamine). It was shown that mutation of a single gene, encoding alpha-mannosidase II, which regulates the hybrid to complex branching pattern of extracellular N-glycans, results in a systemic autoimmune disease similar to human systemic lupus erythematosus [26]. Thus, seropositive RA was characterized by altered glycopattern, attributable to autoimmune and inflammatory conditions, while this was not true in seronegative RA. Seropositive group also was characterized by higher level of systemic inflammation, if judged by C-reactive protein level, confirming previous data that increased AAL exposure on IgG can results from inflammatory processes [24], currently not well understood. Recent data have reported the increase of N-glycosylation sites on variable regions of anti-citrullinated protein antibody (ACPA) due to somatic hypermutations as a common feature of autoimmune diseases [27]. On ACPA antibodies, these Fab glycans carry glycoforms with bisecting GlcNAc residues [28] and thus increase in specific autoimmune-attributable antibody bearing altered glycosylation can be another explanation of the observed phenomena.