scholarly journals Progesterone and Interferon-τ Regulate Cystatin C in the Endometrium

Endocrinology ◽  
2006 ◽  
Vol 147 (7) ◽  
pp. 3478-3483 ◽  
Author(s):  
Gwonhwa Song ◽  
Thomas E. Spencer ◽  
Fuller W. Bazer
Keyword(s):  
Cystatin C ◽  
Fold Increase ◽  
Cysteine Proteases ◽  
Glandular Epithelium ◽  
Luminal Epithelium ◽  
Cathepsin Activity ◽  
Lysosomal Cysteine Proteases ◽  
D 20 ◽  
D 12 ◽  
Ovine Uterus

Cystatin C (CST3) is a secreted inhibitor of lysosomal cysteine proteases cathepsins B (CTSB) and CTSL, which are abundant in the ovine endometrium and conceptus. In mice, cathepsins and cystatins play important roles in implantation and placentation. This study determined effects of the estrous cycle, pregnancy, progesterone (P4), and interferon-τ (IFNT) on CST3 in the ovine uterus. In cyclic ewes, CST3 mRNA was low on d 10, increased about 12-fold by d 12, and declined thereafter. In early pregnant ewes, CST3 mRNA was low on d 10 and increased about 130-fold from d 10 to d 20. CST3 mRNA and protein were abundant in the endometrial luminal epithelium (LE) and glandular epithelium and also in conceptus trophectoderm. In uterine flushes from pregnant ewes, CST3 protein was not detected on d 10 but was abundant on d 12, 14, and 16. In another study, treatment of ovariectomized, cyclic ewes with P4 induced a 14-fold increase in endometrial CST3 mRNA, and IFNT stimulated an additional 2-fold increase in CST3 mRNA in P4-treated ewes but not in ewes treated with P4 and the antiprogestin ZK 136,317. CST3 mRNA and protein were abundant in the endometrial luminal epithelium and superficial glandular epithelium of P4-treated ewes but were very low or not detectable in endometria of P4- and ZK-treated ewes. These results indicate that CST3 is a novel P4-induced and IFNT-stimulated gene expressed only in the epithelial cells of the ovine endometrium and implicate CST3 in regulation of uterine cathepsin activity during conceptus implantation.

scholarly journals Cathepsins in the Ovine Uterus: Regulation by Pregnancy, Progesterone, and Interferon Tau

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4825-4833 ◽  
Author(s):  
Gwonhwa Song ◽  
Thomas E. Spencer ◽  
Fuller W. Bazer
Keyword(s):  
Extracellular Matrix ◽  
Expression Patterns ◽  
Glandular Epithelium ◽  
Luminal Epithelium ◽  
Interferon Tau ◽  
Spatial Expression ◽  
Intracellular Proteins ◽  
Temporal And Spatial ◽  
D 12 ◽  
Ovine Uterus

Cathepsins (CTS) are peptidases that have biological roles in degrading extracellular matrix, catabolism of intracellular proteins, and processing of prohormones. Expression of CTSB, CTSD, CTSH, CTSK, CTSL, CTSS, and CTSZ genes was detected in the endometria of cyclic and early pregnant ewes with distinct temporal and spatial expression patterns. In the d 18 and 20 conceptus, expression of CTSB, CTSD, CTSL, and CTSZ mRNA was detected in the trophectoderm. Of particular note, CTSL mRNA was the most abundant CTS mRNA in the ovine endometrium and detected only in the luminal epithelium and superficial glandular epithelium of cyclic and pregnant ewes. CTSL mRNA increased 8-fold between d 10 and 18 in endometria of pregnant ewes, whereas it declined between d 14 and 16 in cyclic ewes. CTSL protein was also detected in conceptus trophectoderm, and pro-CTSL was detected in uterine flushings from ewes between d 12 and 16 of pregnancy. In ovariectomized and catheterized ewes, CTSL mRNA in the endometrium was increased by progesterone and intrauterine injections of ovine interferon (IFN)τ. Other endometrial CTS genes were also regulated by progesterone alone (CTSB, CTSK, CTSS, and CTSZ) or progesterone and IFNτ (CTSH, CTSK, CTSS, and CTSZ). These results indicate that CTS of endometrial and conceptus origin may regulate endometrial remodeling and conceptus implantation, endometrial CTS genes are regulated by ovarian and placental hormones, and CTSL is a novel IFNτ-stimulated gene expressed only in luminal epithelium and superficial glandular epithelium of the endometrium.

scholarly journals 260 Effects of iron administration timing on pre-weaning performance and hematological criteria in pigs

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 88-89
Author(s):  
Hayden E Williams ◽  
Ryan T Maurer ◽  
Brittany Carrender ◽  
Joel M DeRouchey ◽  
Jason C Woodworth ◽  
...  
Keyword(s):  
Growth Performance ◽  
Animal Health ◽  
Injection Timing ◽  
Iron Administration ◽  
Newborn Pigs ◽  
Pig Performance ◽  
D 20 ◽  
D 12 ◽  
Administration Timing

Abstract Newborn pigs (n=1,892; 1.5 kg BW) were used in a 20-d study evaluating the effects of Fe injection timing after birth on preweaned pig performance and blood criteria. A total of 172 litters were used. One d after farrowing, piglets were weighed, and 11 pigs within each litter were allotted to 1 of 6 treatments in a CRD. Treatments consisted of pigs receiving no Fe injection or 200-mg of injectable Fe (GleptoForte, Ceva Animal Health, Lenexa, KS) provided on d 1, 3, 5, or 7 of age, or 200-mg on d 1 plus 200-mg on d 12. 1 pig/litter received no Fe injection and 2 pigs/litter were placed on all other treatments. Piglets were weighed on d 1 and 20 after birth to determine growth performance and bled on d 20 to determine Fe status. Increasing the age that piglets received the Fe injection tended to decrease (linear; P=0.080) ADG. Not providing an Fe injection decreased (P=0.0001) overall ADG and d 20 BW compared to all other treatments. Hemoglobin and Hct decreased (linear; P< 0.05) with increasing age when pigs received an Fe injection. There was no evidence of differences (P >0.10) between the pigs receiving a 200-mg injection on d 1 and d 12 compared to those receiving the Fe on d 1 only. Pigs not provided an Fe injection had decreased (P=0.0001) Hb and Hct values compared to pigs receiving an Fe injection. Pigs receiving the 200-mg injection on d 1 and 12 had increased (P=0.0001) Hb and Hct values compared to pigs receiving 200-mg on d 1 only. Results suggest that providing a 200-mg Fe injection within 7 d after farrowing is sufficient for optimizing preweaning growth performance. The additional 200-mg Fe injection at d 12 did not influence growth performance but does increase Hb and Hct at weaning.

scholarly journals Overexpression of Plasmodium falciparum M1 Aminopeptidase Promotes an Increase in Intracellular Proteolysis and Modifies the Asexual Erythrocytic Cycle Development

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1452
Author(s):  
Carolina C. Hoff ◽  
Mauro F. Azevedo ◽  
Adriana B. Thurler ◽  
Sarah El Chamy Maluf ◽  
Pollyana M. S. Melo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Fold Increase ◽  
Cysteine Proteases ◽  
Aminopeptidase Activity ◽  
Lower Sensitivity ◽  
Wild Type ◽  
Erythrocytic Cycle ◽  
Transgenic Parasite

Plasmodium falciparum, the most virulent of the human malaria parasite, is responsible for high mortality rates worldwide. We studied the M1 alanyl-aminopeptidase of this protozoan (PfA-M1), which is involved in the final stages of hemoglobin cleavage, an essential process for parasite survival. Aiming to help in the rational development of drugs against this target, we developed a new strain of P. falciparum overexpressing PfA-M1 without the signal peptide (overPfA-M1). The overPfA-M1 parasites showed a 2.5-fold increase in proteolytic activity toward the fluorogenic substrate alanyl-7-amido-4-methylcoumarin, in relation to the wild-type group. Inhibition studies showed that overPfA-M1 presented a lower sensitivity against the metalloaminopeptidase inhibitor bestatin and to other recombinant PfA-M1 inhibitors, in comparison with the wild-type strain, indicating that PfA-M1 is a target for the in vitro antimalarial activity of these compounds. Moreover, overPfA-M1 parasites present a decreased in vitro growth, showing a reduced number of merozoites per schizont, and also a decrease in the iRBC area occupied by the parasite in trophozoite and schizont forms when compared to the controls. Interestingly, the transgenic parasite displays an increase in the aminopeptidase activity toward Met-, Ala-, Leu- and Arg-7-amido-4-methylcoumarin. We also investigated the potential role of calmodulin and cysteine proteases in PfA-M1 activity. Taken together, our data show that the overexpression of PfA-M1 in the parasite cytosol can be a suitable tool for the screening of antimalarials in specific high-throughput assays and may be used for the identification of intracellular molecular partners that modulate their activity in P. falciparum.

scholarly journals In vitro effects of L-arginine on lysosomal cysteine proteases activity in isolated experiment and in the state of oxidative stress

2015 ◽  
Vol 96 (5) ◽  
pp. 876-882
Author(s):  
M A Fomina ◽  
A M Kudlaeva
Keyword(s):  
Oxidative Stress ◽  
Sucrose Solution ◽  
Membrane Damage ◽  
Cysteine Proteases ◽  
Lysosomal Membranes ◽  
In Vitro Incubation ◽  
Cathepsin H ◽  
Lysosomal Cysteine Proteases ◽  
Stimulation Of

Aim. Assessment of direct influence of arginine on lysosomal cysteine proteases activity in vitro, in isolation as well as the stimulation of oxidative stress. Methods. The study was conducted on the 72 female conventional mature Wistar rats 280-320 g divided into 6 series of 12 rats each. Lysosome slurries were isolated from the liver of intact animals with a subsequent in vitro incubation in a sucrose solution, in the presence of L-arginine, as well as in the presence of L-arginine accompanied by the stimulation of oxidative stress. Samples of control groups were exposed in vitro with the addition of isolate and oxidant, respectively. Each batch was reproduced three times, incubation was performed at 37 °C in a water bath for 1, 2 and 4 hours. The activity of cathepsins B, L and H was studied using spectrofluorimetric method in two fractions - intra- and extralysosomal. Acid phosphatase activity was used as the main marker of membrane labialization. Results. One hour Incubation with 5 mM arginine in vitro led to inhibition of the cathepsin H activity and lysosomal membrane damage, however, further increase in incubation time led to its stabilization. In vitro exposure to 5 mM H2O2 caused an increase in activity of cathepsines B and L and the drop in the cathepsin H activity without obvious changes in the distribution of enzymes between extra and intralysosomal fractions. In a state of oxidative stress 2-hour in vitro incubation with 5 mM arginine reduced the permeability of lysosomal membranes for cathepsines B, H and L; while 4-hour incubation led to the destabilization of lysosomal membranes. Conclusion. The direct effect of arginine at a concentration of 5 mM within the 1,2 and 4-hour time intervals leads to a distinct change as a lysosomal cysteine protease activity and stability of lysosomal membranes.

scholarly journals Tight and Adherens Junctions in the Ovine Uterus: Differential Regulation by Pregnancy and Progesterone

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3922-3931 ◽  
Author(s):  
M. Carey Satterfield ◽  
Kathrin A. Dunlap ◽  
Kanako Hayashi ◽  
Robert C. Burghardt ◽  
Thomas E. Spencer ◽  
...  
Keyword(s):  
Tight Junction ◽  
Adherens Junctions ◽  
Luminal Epithelium ◽  
Tissue Fluid ◽  
Tight Junction Formation ◽  
Junction Protein ◽  
Conceptus Development ◽  
Associated Proteins ◽  
Continuous Presence ◽  
D 12

In species with noninvasive implantation by conceptus trophectoderm, fetal/maternal communications occur across the endometrial epithelia. The present studies identified changes in junctional complexes in the ovine endometrium that regulate paracellular trafficking of water, ions, and other molecules, and the secretory capacity of the uterine epithelia. Distinct temporal and spatial alterations in occludin, tight junction protein 2, and claudin 1–4 proteins were observed in the endometrium of cyclic and early pregnant ewes. Dynamic changes in tight junction formation were characterized by an abundance of tight junction proteins on d 10 of the estrous cycle and pregnancy that substantially decreased by d 12. Early progesterone administration advanced conceptus development on d 9 and 12 that was associated with loss of tight-junction-associated proteins. Pregnancy increased tight-junction-associated proteins between d 14–16. Cadherin 1 and β-catenin, which form adherens junctions, were abundant in the endometrial glands, but decreased after d 10 of pregnancy in the luminal epithelium and then increased by d 16 with the onset of implantation. Results support the ideas that progesterone elicits transient decreases in tight and adherens junctions in the endometrial luminal epithelium between d 10–12 that increases selective serum and tissue fluid transudation to enhance blastocyst elongation, which is subsequently followed by an increase in tight and adherens junctions between d 14–16 that may be required for attachment and adherence of the trophectoderm for implantation. The continuous presence of tight and adherens junctions in the uterine glands would allow for vectorial secretion of trophic substances required for conceptus elongation and survival.

scholarly journals 152 Effects of dietary lactose level on nursery pig performance

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 86-87
Author(s):  
Jason Frank ◽  
Emily Sholtz ◽  
Casey Neill ◽  
Jon De Jong
Keyword(s):  
Linear Trend ◽  
Phase 1 ◽  
Phase 2 ◽  
Feed Cost ◽  
Nursery Pig ◽  
Quadratic Response ◽  
Weaned Pig ◽  
Pig Performance ◽  
D 20 ◽  
D 12

Abstract Lactose is a critical nutrient in post weaning diets to help pigs transition from sows’ milk to dry feed. The objective of this study was to evaluate the effects of increasing dietary lactose level on nursery pig performance. For this trial 1,080 weaned pigs (PIC 359 x 1050; BW = 6.24 kg; 21 d) were fed 5 lactose programs using a feed budget. Program A = 24, 18, 7%; B = 20, 14, 5%; C =16, 10, 3%; D = 12, 6, 1%; and E = 8, 2, 0% lactose for Phase 1, 2, and 3; respectively. The feed budget for Phase 1 (d 0–7), 2 (d 7–14), and 3 (d 14–20) was 0.91, 3.4, and 4.5 kg/pig; respectively. A common Phase 4 (d 20–48) diet (0% lactose) was fed ad libitum. There was a quadratic response to lactose level in treatments A through E for Phase 1 ADFI (89, 71, 73, 73, 89 g/d; respectively, P = 0.034) and G:F (1.09, 1.33, 1.14, 1.15, 0.91; respectively, P = 0.042). Treatment A through E Phase 1 ADG was 100, 95, 91, 82, and 82 g/d, and Phase 2 ADG (Linear, P = 0.023) was 322, 313, 318, 304, and 295 g/d; respectively. The result was a linear trend for increased BW at the end of Phase 2 (P = 0.10) for treatments A through E (9.21, 9.10, 9.16, 9.00, 8.86 kg; respectively). Although feed cost/pig increased as lactose level increased (Linear, P = 0.041), there was no significant response in margin over feed cost/pig during the overall nursery period for treatments A through E ($15.31, $16.41, $16.22, $15.87, $16.04; respectively). In conclusion, pig performance improved during Phase 1 and 2 with increasing level of dietary lactose. These results confirm previous research showing the importance of dietary lactose in weaned pig diets.

Correction to: Stabilized Human Cystatin C, Variant L47C/G69C, is a Better Reporter than the Wild-type Inhibitor for Characterizing the Thermodynamics of Binding to Cysteine Proteases

2019 ◽  
Vol 38 (5) ◽  
pp. 608-608
Author(s):  
David O. Tovar-Anaya ◽  
L. Irais Vera-Robles ◽  
M. Teresa Vieyra-Eusebio ◽  
Ponciano García-Gutiérrez ◽  
Francisco Reyes-Espinosa ◽  
...  
Keyword(s):  
Cystatin C ◽  
Cysteine Proteases ◽  
Wild Type ◽  
Human Cystatin C ◽  
Human Cystatin
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