scholarly journals Cysteine-rich granulin-3 rapidly promotes amyloid-β fibrils in both redox states

2019 ◽  
Vol 476 (5) ◽  
pp. 859-873 ◽  
Author(s):  
Anukool A. Bhopatkar ◽  
Gaurav Ghag ◽  
Lauren M. Wolf ◽  
Dexter N. Dean ◽  
Melissa A. Moss ◽  
...  

Abstract Granulins (GRNs 1–7) are cysteine-rich proteolytic products of progranulin (PGRN) that have recently been implicated in neurodegenerative diseases including frontotemporal dementia (FTD) and Alzheimer's disease (AD). Their precise mechanism in these pathologies remains uncertain, but both inflammatory and lysosomal roles have been observed for GRNs. Among the seven GRNs, GRN-3 is well characterized and is implicated within the context of FTD. However, the relationship between GRN-3 and amyloid-β (Aβ), a protein relevant in AD pathology, has not yet been explored. To gain insight into this mechanism, we investigated the effect of both oxidized and reduced GRN-3 on Aβ aggregation and found that both GRN-3 (oxidized) and rGRN-3 (reduced) bind to monomeric and oligomeric Aβ42 to promote rapid fibril formation with subtle rate differences. As low molecular weight oligomers of Aβ are well-established neurotoxins, rapid promotion of fibrils by GRN-3 mitigates Aβ42-induced cellular apoptosis. These data provide valuable insights in understanding GRN-3's ability to modulate Aβ-induced toxicity under redox control and presents a new perspective toward AD pathology. These results also prompt further investigation into the role(s) of other GRNs in AD pathogenesis.

1998 ◽  
Vol 8 (3) ◽  
pp. 347-355 ◽  
Author(s):  
Mary Bettey ◽  
W. E. Finch-Savage

AbstractPlants respond to sub-optimal conditions by the synthesis of specific ‘stress’ proteins, and these are thought to play a role in stress tolerance. Some of these proteins accumulate during late seed development, arguably to protect against damage during post-maturation drying and subsequent imbibition, prior to germination. Seed vigour is also determined during this late stage of seed development. High vigour seeds are those that can withstand the desiccation required for storage and successfully germinate under sub-optimal conditions to establish healthy seedlings. If stress proteins are involved in tolerating stress conditions, then they are likely to be important determinants of seed vigour. In this work the relationship between seed vigour (measured by seed germination performance following rapid aging, or under water stress) in Brassica oleracea var. capitata and the content of two classes of stress protein (dehydrins and a low molecular weight heat shock protein HSP17.6) at maturity was examined. Dehydrins did not show a positive relationship with seed performance. However, the protein HSP17.6 showed a positive correlation with seed performance, and a treatment that reduced the amount of this protein in the seed also caused a reduction in subsequent seed performance.


1975 ◽  
Vol 228 (4) ◽  
pp. 1020-1023 ◽  
Author(s):  
CJ Hahn ◽  
GW Evans

The effects of zinc deficiency on the whole-body absorption and intestinal content of Zn, Cd, Cu, Co, Fe, Mn, and Cr were determined in the rat 1 h after oral administration of the isotopes. Both the absorption and intestinal content of Zn and Cr were increased in zinc-deficient rats, and the intestinal content of Feand Co was also increased in the zinc-deficient animals. Zinc administered orally with Cr decreased both absorption and intestinal content of the isotope in zinc-deficient rats. Chromium administered orally with Zn decreased intestinal content and absorption of Zn in zinc-deficient rats. Fractionation of mucosal supernatants by gel filtration showed that both zinc and chromium eluted in the same low molecular weight fraction. The elution patterns of zinc and cadmium from that of zinc-supplemented animals. These experiments provide some insight into the specificity of the zinc absorption pathway and present some explanations for the interaction or lack of interaction among trace elements.


1974 ◽  
Vol 62 (2) ◽  
pp. 355-361 ◽  
Author(s):  
JENNIFER M. DEHNEL ◽  
P. D. McCONAGHEY ◽  
M. J. O. FRANCIS

SUMMARY Plasma somatomedin is the intermediary through which growth hormone (GH) exerts its effects on the growing skeleton. Somatomedin activity may be produced in vitro by perfusion of the liver and kidneys of rats with Waymouth's medium containing GH. The relationship between the activity of plasma somatomedin and somatomedin of hepatic and renal origin has yet to be clarified. Somatomedin from plasma can be separated into active fractions of both high and low molecular weight. Similarly, ultrafiltration of medium containing somatomedin of hepatic origin indicates the existence of two active fractions, one of high molecular weight (greater than 50000) and one of low molecular weight (less than 1000). The latter can be attributed to the release of amino acids, such as serine and glutamine, by the perfused tissue. The high molecular weight fraction is believed to represent GH-dependent somatomedin. Fractions that inhibit production of cartilage matrix are present in liver perfusates as well as in plasma. These results provide further evidence that the liver is a source of GH-dependent somatomedin in vivo. Furthermore, cartilage growth may be controlled not only by the GH-stimulated release of somatomedin by the liver, but also by its release of acid-labile somatomedin inhibitors.


2015 ◽  
Vol 6 (12) ◽  
pp. 1972-1980 ◽  
Author(s):  
Thomas L. Williams ◽  
Jin-Kyu Choi ◽  
Krystyna Surewicz ◽  
Witold K. Surewicz

1989 ◽  
Vol 40 (3) ◽  
pp. 685
Author(s):  
GJ Harvey

The relationship between molecular structure and biological efficacy was investigated for 16 esters of 2,4-D [(2,4-dich1orophenoxy)acetic acid] on rubber vine (Cryptostegia grandiflora). These included the normal (n) or straight-chain esters from C-1 (methyl) to C-8 (octyl), the n-decyl, n-dodecyl, isobutyl, amyl (iso-pentyl), 2-ethylhexyl (iso-octyl), and the methoxy-, ethoxy-, and butoxyethyl esters. For the normal series esters, biological efficacy was found to be a function of both the molecular weight and the vapour pressure of the esters. This relationship was linear for the higher molecular weight, low volatile esters, biological efficacy decreasing with increasing molecular weight and the accompanying decrease in vapour pressure of the esters. The low molecular weight, volatile esters were more active than the higher molecular weight, low volatile esters, and increases in the vapour pressure of these low molecular weight, volatile esters were sufficient to account for the deviation from linearity of those esters. When all esters are considered, the same relationships hold but the branched-chain (iso) and chemically substituted (alkoxy alcohol) esters are less effective than the corresponding normal esters. Possible reasons for these results are discussed.


2019 ◽  
Vol 7 (4) ◽  
pp. 108
Author(s):  
Yeo Ok Han ◽  
Yunju Jeong ◽  
Hyun Ju You ◽  
Seockmo Ku ◽  
Geun Eog Ji ◽  
...  

Rotavirus infection is the most common diarrheal disease worldwide in children under five years of age, and it often results in death. In recent years, research on the relationship between rotavirus and probiotics has shown that probiotics are effective against diarrhea. A clinical trial has reported that Bifidobacterium longum BORI reduced diarrhea induced by rotavirus. The present work investigated the anti-rotaviral effect of B. longum BORI by cytopathic effect observation and real time cell analyses. Our study found that B. longum BORI showed strong anti-rotaviral effect when incubated with MA104 cells prior to viral infection, suggesting that the probiotic does in fact interfere with the interaction of viruses and host cells. It is believed that the efficacy is due to low-molecular weight and non-protein components derived from B. longum BORI. This discovery can help broaden the industrial application of B. longum BORI, which has been proven to be a safe and effective probiotic.


2014 ◽  
Vol 8 ◽  
pp. CMO.S13386 ◽  
Author(s):  
Miguel Barbosa

The relationship between venous thromboembolism and cancer has been known for many years, and there is solid scientific evidence addressing the adequate treatment of this condition in oncology patients. However, established prescribing habits, individual patient challenges, and uncertainty concerning treatment justifies poor adherence to published guidelines. This paper reviews venous thromboembolism treatment while focusing on vitamin K antagonists, low-molecular-weight heparins, and novel oral anticoagulants, namely in terms of their efficacy and limitations.


2014 ◽  
Vol 11 (16) ◽  
pp. 4407-4414 ◽  
Author(s):  
Y. Miyazaki ◽  
M. Sawano ◽  
K. Kawamura

Abstract. Lactic acid (LA) and glycolic acid (GA), which are low-molecular-weight hydroxyacids, were identified in the particle and gas phases within the marine atmospheric boundary layer over the western subarctic North Pacific. A major portion of LA (81%) and GA (57%) was present in the particulate phase, which is consistent with the presence of a hydroxyl group in these molecules leading to the low volatility of the compounds. The average concentration (±SD) of LA in more biologically influenced marine aerosols (33 ± 58 ng m−3) was substantially higher than that in less biologically influenced aerosols (11 ± 12 ng m−3). Over the oceanic region of phytoplankton blooms, the concentration of aerosol LA was comparable to that of oxalic acid, which was the most abundant diacid during the study period. A positive correlation was found between the LA concentrations in more biologically influenced aerosols and chlorophyll a in seawater (r2 = 0.56), suggesting an important production of aerosol LA possibly associated with microbial (e.g., lactobacillus) activity in seawater and/or aerosols. Our finding provides a new insight into the poorly quantified microbial sources of marine organic aerosols (OAs) because such low-molecular-weight hydroxyacids are key intermediates for OA formation.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kenji Sakurai ◽  
Takeshi Saito ◽  
Hiromi Hosoya ◽  
Yoshitaka Kurihara ◽  
Kaori Kurosawa ◽  
...  

Abstract Background and Aims The purpose of hemodiafiltration (HDF) is to remove small- to large molecular weight solutes in order to prevent and treat complications and to improve the prognosis of dialysis patients. Especially, larger low molecular weight proteins (LMWPs) must be removed efficiently. β2-microglobulin (MG) (molecular weight [MW], 11.8 kDa: Stokes radius, 15.6A), is considered as an important marker of dialysis efficiency. However, MW of β2-MG is too small as a marker in HDF. Conversely, α1-MG (MW, 33 kDa: Stokes radius, 28.4A) is the most appropriate marker for evaluation of solute removal efficiency of HDF because of the following reasons: (1) optical molecular size; (2) not very low physiological blood concentration; (3) stable production rate; (4) removal by convection; and (5) accumulation in ESRD. Efficient removal of α1-MG without losing albumin (Alb) (MW,66 kDa: Stokes radius, 35.5A) is impossible even by HDF. In this study, we investigated the relationship between LMWP removal efficiencies and the volume of Alb leakage by analyzing the results of patients undergoing HDF. And we also evaluated the trend of the serum levels of patients who had received high-efficiency HDF for more than three years Method Eighty-seven patients who had received HDF in 2018–2019 were included. The results of HDF (a total of 435 sessions) were analyzed (blood flow rate, 261.5±28.5 mL/min; replacement fluid volume, 48.7 L/s pre-dilution on-line HDF and 14.2 L/s post-dilution on-line HDF). The removal efficiencies of β2-MG, prolactin (PRL), and α1-MG, and the volume of Alb leakage were examined. In addition, the relationship between the removal efficiency of each solute and the volume of Alb leakage was investigated. Changes in serum Alb level were analyzed in 13 patients who continued to receive high-efficiency HDF (the removal rate of α1-MG was 30% or more) for more than three years. Results Analysis of the results (mean ± SD) obtained from a total of 435 sessions (87 patients) showed that the removal rates of β2-MG, PRL, and α1-MG were 80.7 ± 4.5%, 75.8±9.4 and 33.8 ± 9.4%, respectively, and the Alb leakage was 3.9 ± 1.8 g/s. The equations of the approximate curve between Alb leakage and β2-MG, PRL, and α1-MG removal rates were expressed as follows: ï½™= 1.4197ln(x) + 78.972 (R2 = 0.0426), y = 9.7185ln(x) + 64.134 (R2 =0.4632), and ï½™™= 11.225ln(x) + 20.282 (R2 = 0.6191), respectively. These results indicate that the dynamics between Alb leakage and α1-MG removal are very similar. That is, although the molecular weight of Alb is twice as that of α1-MG, the difference in their Stokes radius is 20%; therefore, separate removal of Alb and α1-MG is impossible. The mean serum Alb level in 13 patients who received high-efficiency HDF for 3 years or longer was 3.59 ± 0.23 g/dL in January 2017 and 3.69 ± 0.28 g/dL in December 2019, revealing no changes. Conclusion The efficient removal of larger LMWPs leads to the leakage of Alb. However, an Alb leakage of 3 to 6 g/s has little influence on the serum Alb level of patients. Thus, α1-MG is the most appropriate marker of the solute removal efficiency of HDF.


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