scholarly journals METABOLISM AND FUNCTION OF GAMMA GLOBULIN IN ALEUTIAN DISEASE OF MINK

1965 ◽  
Vol 121 (6) ◽  
pp. 889-900 ◽  
Author(s):  
David D. Porter ◽  
Frank J. Dixon ◽  
Austin E. Larsen

Aleutian disease-affected mink, which are markedly hypergammaglobulinemic, show a decreased half-life of the serum gamma globulin indicating that the hyperglobulinemia is due to increased production. No evidence that the gamma globulin was antibody to the infectious agent, to autologous or isologous tissues, or to antigens the animal was responding to prior to development of the disease was obtained. The increased gamma globulin was found to be of the 6.4S variety, and gamma globulin containing protein-protein complexes of 9S to 17S and 22S to 25S classes were observed in serums of affected mink. The findings are most consistent with the Aleutian disease virus acting as a direct and somewhat selective stimulus to plasma cell proliferation. There is no evidence that the arterial and glomerular lesions of Aleutian disease have an immunologic pathogenesis. It seems possible that these vascular changes may be directly caused by the viral agent, or may be the result of the increased gamma globulin levels.

Author(s):  
C.A. Mannella ◽  
K.F. Buttle ◽  
K.A. O‘Farrell ◽  
A. Leith ◽  
M. Marko

Early transmission electron microscopy of plastic-embedded, thin-sectioned mitochondria indicated that there are numerous junctions between the outer and inner membranes of this organelle. More recent studies have suggested that the mitochondrial membrane contacts may be the site of protein complexes engaged in specialized functions, e.g., import of mitochondrial precursor proteins, adenine nucleotide channeling, and even intermembrane signalling. It has been suggested that the intermembrane contacts may be sites of membrane fusion involving non-bilayer lipid domains in the two membranes. However, despite growing interest in the nature and function of intramitochondrial contact sites, little is known about their structure.We are using electron microscopic tomography with the Albany HVEM to determine the internal organization of mitochondria. We have reconstructed a 0.6-μm section through an isolated, plasticembedded rat-liver mitochondrion by combining 123 projections collected by tilting (+/- 70°) around two perpendicular tilt axes. The resulting 3-D image has confirmed the basic inner-membrane organization inferred from lower-resolution reconstructions obtained from single-axis tomography.


2016 ◽  
pp. 126-129
Author(s):  
M. Makarenko ◽  
◽  
D. Hovsyeyev ◽  
L. Sydoryk ◽  
◽  
...  

Different kinds of physiological stress cause mass changes in the cells, including the changes in the structure and function of the protein complexes and in separate molecules. The protein functions is determined by its folding (the spatial conclusion), which depends on the functioning of proteins of thermal shock- molecular chaperons (HSPs) or depends on the stress proteins, that are high-conservative; specialized proteins that are responsible for the correct proteinaceous folding. The family of the molecular chaperones/ chaperonins/ Hsp60 has a special place due to the its unique properties of activating the signaling cascades through the system of Toll-like receptors; it also stimulates the cells to produce anti- inflammatory cytokines, defensins, molecules of cell adhesion and the molecules of MHC; it functions as the intercellular signaling molecule. The pathological role of Hsp60 is established in a wide range of illnesses, from diabetes to atherosclerosis, where Hsp60 takes part in the regulation of both apoptosis and the autoimmune processes. The presence of the HSPs was found in different tissues that are related to the reproductive system. Key words: molecular chaperons (HSPs), Toll-like receptors, reproductive function, natural auto antibody.


2020 ◽  
Author(s):  
Jeongkyung Lee ◽  
Ruya Liu ◽  
Byung S. Kim ◽  
Yiqun Zhang ◽  
Feng Li ◽  
...  

2021 ◽  
Vol 4 (3) ◽  
pp. 51
Author(s):  
Satish Kantipudi ◽  
Daniel Harder ◽  
Sara Bonetti ◽  
Dimitrios Fotiadis ◽  
Jean-Marc Jeckelmann

Heterodimeric amino acid transporters (HATs) are protein complexes composed of two subunits, a heavy and a light subunit belonging to the solute carrier (SLC) families SLC3 and SLC7. HATs transport amino acids and derivatives thereof across the plasma membrane. The human HAT 4F2hc-LAT1 is composed of the type-II membrane N-glycoprotein 4F2hc (SLC3A2) and the L-type amino acid transporter LAT1 (SLC7A5). 4F2hc-LAT1 is medically relevant, and its dysfunction and overexpression are associated with autism and tumor progression. Here, we provide a general applicable protocol on how to screen for the best membrane transport protein-expressing clone in terms of protein amount and function using Pichia pastoris as expression host. Furthermore, we describe an overexpression and purification procedure for the production of the HAT 4F2hc-LAT1. The isolated heterodimeric complex is pure, correctly assembled, stable, binds the substrate L-leucine, and is thus properly folded. Therefore, this Pichia pastoris-derived recombinant human 4F2hc-LAT1 sample can be used for downstream biochemical and biophysical characterizations.


2020 ◽  
Vol 29 ◽  
pp. 096368972091830 ◽  
Author(s):  
Ping Zhou ◽  
Andrew Irving ◽  
Huifang Wu ◽  
Juan Luo ◽  
Johana Aguirre ◽  
...  

Given the crucial role of microRNAs in the cellular proliferation of various types of cancers, we aimed to analyze the expression and function of a cellular proliferation-associated miR-188-5p in papillary thyroid carcinoma (PTC). Here we demonstrate that miR-188-5p is downregulated in PTC tumor tissues compared with the associated noncancerous tissues. We also validate that the miR-188-5p overexpression suppressed the PTC cancer cell proliferation. In addition, fibroblast growth factor 5 (FGF5) is observed to be downregulated in the PTC tumor tissues compared with the associated noncancerous tissues. Subsequently, FGF5 is identified as the direct functional target of miR-188-5p. Moreover, the silencing of FGF5 was found to inhibit PTC cell proliferation, which is the same pattern as miR-188-5p overexpression. These results suggest that miR-188-5p-associated silencing of FGF5 inhibits tumor cell proliferation in PTC. It also highlights the importance of further evaluating miR-188-5p as a potential biomarker and therapy target in PTC.


2001 ◽  
Vol 6 (12) ◽  
pp. 1055-1066 ◽  
Author(s):  
Keigyou Yoh ◽  
Takehiko Sugawara ◽  
Hozumi Motohashi ◽  
Yousuke Takahama ◽  
Akio Koyama ◽  
...  

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Nicolas J. Delalez ◽  
Richard M. Berry ◽  
Judith P. Armitage

ABSTRACTSome proteins in biological complexes exchange with pools of free proteins while the complex is functioning. Evidence is emerging that protein exchange can be part of an adaptive mechanism. The bacterial flagellar motor is one of the most complex biological machines and is an ideal model system to study protein dynamics in large multimeric complexes. Recent studies showed that the copy number of FliM in the switch complex and the fraction of FliM that exchanges vary with the direction of flagellar rotation. Here, we investigated the stoichiometry and turnover of another switch complex component, FliN, labeled with the fluorescent protein CyPet, inEscherichia coli. Our results confirm that,in vivo, FliM and FliN form a complex with stoichiometry of 1:4 and function as a unit. We estimated that wild-type motors contained 120 ± 26 FliN molecules. Motors that rotated only clockwise (CW) or counterclockwise (CCW) contained 114 ± 17 and 144 ± 26 FliN molecules, respectively. The ratio of CCW-to-CW FliN copy numbers was 1.26, very close to that of 1.29 reported previously for FliM. We also measured the exchange of FliN molecules, which had a time scale and dependence upon rotation direction similar to those of FliM, consistent with an exchange of FliM-FliN as a unit. Our work confirms the highly dynamic nature of multimeric protein complexes and indicates that, under physiological conditions, these machines might not be the stable, complete structures suggested by averaged fixed methodologies but, rather, incomplete rings that can respond and adapt to changing environments.IMPORTANCEThe flagellum is one of the most complex structures in a bacterial cell, with the core motor proteins conserved across species. Evidence is now emerging that turnover of some of these motor proteins depends on motor activity, suggesting that turnover is important for function. The switch complex transmits the chemosensory signal to the rotor, and we show, by using single-cell measurement, that both the copy number and the fraction of exchanging molecules vary with the rotational bias of the rotor. When the motor is locked in counterclockwise rotation, the copy number is similar to that determined by averaged, fixed methodologies, but when locked in a clockwise direction, the number is much lower, suggesting that that the switch complex ring is incomplete. Our results suggest that motor remodeling is an important component in tuning responses and adaptation at the motor.


2009 ◽  
Vol 20 (11) ◽  
pp. 2317-2326 ◽  
Author(s):  
Zhen-Mei Liu ◽  
Soo-Yeon Lee ◽  
Sukhéna Sarun ◽  
Dieter Peschel ◽  
Thomas Groth

2021 ◽  
Author(s):  
Junhua Gong ◽  
Minghua Cong ◽  
Hao Wu ◽  
Menghao Wang ◽  
He Bai ◽  
...  

Abstract Background The capacity of the liver to restore its architecture and function assures good prognoses of patients who suffer serious hepatic injury or cancer resection. In our study, we found that the P53/miR-34a/SIRT1 positive feedback loop has a remarkable negative regulatory effect, which is related to the termination of liver regeneration. Here, we described how P53/miR-34a/SIRT1 positive feedback loop controls liver regeneration and its possible relationship with liver cancer.Method We performed partial hepatectomy (PH) in mice transfected with adenovirus (Ade) overexpressing P53 and adenovirus-associated virus (AAV) knock-downing miR-34a. LR was analyzed by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were investigated. Bile acid (BA) levels during LR were analyzed by metabolomics of bile acids. Results We found that the P53/miR-34a/SIRT1 positive feedback loop was activated in the late phase of LR. Overexpression of P53 terminated LR early and enhanced P53/miR-34a/SIRT1 positive feedback loop expression and its proapoptotic effect. Mice from the Ade-P53 group showed smaller livers and higher levels of serum ALT and AST than control mice. While knock-down of miR-34a abolished P53/miR-34a/SIRT1 positive feedback loop during LR. Mice from anti-miR-34a group showed larger livers and lower levels of PCNA-positive cells than control mice. T-β-MCA increased gradually during LR and peaked at 7 days after PH. T-β-MCA inhibited cell proliferation and promoted cell apoptosis via facilitating the P53/miR-34a/SIRT1 positive feedback loop during LR by suppressing FXR/SHP. Conclusion The P53/miR-34a/SIRT1 positive feedback loop plays an important role in the termination of LR. Our findings shed light on the molecular and metabolic mechanisms of LR termination and provide a potential therapeutic alternative for treating P53-wild-type HCC patients.


1981 ◽  
Vol 76 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Ageu Godoy Magalhães Filho ◽  
Antônio Victoriano Barbosa ◽  
Teresa Cristina Ferreira

Twenty one cases of hepatoesplenic schistosomiasis patients without clinical and laboratory evidence of renal disease, were studied by surgical biopsies using light microscopy and immunofluorescence. The cases were classified histologically as: normal pattern (6 cases); minimal changes (6 cases); and mesangial proliferative glomerulonephritis (9 cases). By the immunofluorescence microscopy using anti IgM, IgG, IgA and C3, the predominant finding in all biopsies, except the normal cases, was granular deposits of IgM in the mesangium along with C3. On the other hand, IgG was present in all cases including normal biopsies along the capillary walls. However IgG was also present in the mesangium only in cases with glomerular lesions. This finding may well be similar to that recently described as IgM mesangial nephropathy. According to our cases a mesangial proliferative glomerulonephritis, characterized by segmental cell proliferation and deposition of IgM in the mesangium, is probably the entity found in the early stages of mansonic schistosomiasis.


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