Comparative effects of cathepsin inhibitors on rat embryonic development in vitro. Evidence that cathepsin D is unimportant in the proteolytic function of yolk sac.

Development ◽  
1985 ◽  
Vol 86 (1) ◽  
pp. 271-281
Author(s):  
Stuart J. Freeman ◽  
Nigel A. Brown
Keyword(s):  
Cathepsin D ◽  
Proteinase Inhibitors ◽  
Yolk Sac ◽  
Abnormal Development ◽  
Biochemical Basis ◽  
Early Organogenesis ◽  
Development In Vitro ◽  
Hydrolysis Of ◽  
Severe Growth

The effects of two proteinase inhibitors, leupeptin and pepstatin on the development of 9·5-day rat conceptuses in vitro has been studied. All cultures were of 48 h duration and the inhibitors were present throughout the entire period. When pepstatin was added to the culture medium (5–25 μg/ml) conceptuses developed and grew to an extent that did not differ from untreated controls. However, leupeptin (l–4 μg/ml) caused severe growth retardation and abnormal development of conceptuses. The effects of the two inhibitors on the hydrolysis of 125I-labelled BSA and haemoglobin by homogenates of 10·5-day yolk sac indicated the biochemical basis for the differential toxic effects of the two inhibitors on development. Leupeptin was highly inhibitory of the degration of both substrates whereas pepstatin caused no inhibition of 125I-labelled BSA hydrolysis, and only a slight inhibition of haemoglobin hydrolysis. These observations demonstrate that cathepsin D, a lysosomal aspartic proteinase that is specifically inhibited by pepstatin is not involved in yolk-sac-mediated protein utilization by early organogenesis-phase conceptuses and that lysosomal cysteine proteinases, specifically inhibited by leupeptin, are of paramount importance in this yolk sac function.

Digestive proteinases of the larger black flour beetle, Cynaeus angustus (Coleoptera: Tenebrionidae)

2006 ◽  
Vol 96 (2) ◽  
pp. 167-172 ◽  
Author(s):  
B. Oppert ◽  
P. Walters ◽  
M. Zuercher
Keyword(s):  
Proteinase Inhibitors ◽  
Control Strategies ◽  
Cysteine Proteinase ◽  
Serine Proteinase ◽  
Cysteine Proteinase Inhibitor ◽  
Flour Beetle ◽  
Reducing Conditions ◽  
Caseinolytic Activity ◽  
Hydrolysis Of

AbstractDigestion in the larger black flour beetle, Cynaeus angustus (LeConte), was studied to identify new control methods for this pest of stored grains and grain products. The physiological pH of the larval gut, as measured with extracts in water, was approximately 6.1, and the pH for optimal hydrolysis of casein by gut extracts was 6.2 when buffers were reducing. However, under non-reducing conditions, hydrolysis of casein and synthetic serine proteinase substrates was optimal in alkaline buffer. Three major proteinase activities were observed in zymograms using casein or gelatin. Caseinolytic activity of C. angustus gut extracts was inhibited by inhibitors that target aspartic and serine proteinase classes, with minor inhibition by a cysteine proteinase inhibitor. In particular, soybean trypsin and trypsin/chymotrypsin inhibitors were most effective in reducing the in vitro caseinolytic activity of gut extracts. Based on these data, further studies are suggested on the effects of dietary soybean inhibitors of serine proteinases, singly and in combination with aspartic and cysteine proteinase inhibitors, on C. angustus larvae. Results from these studies can be used to develop new control strategies to prevent damage to grains and stored products by C. angustus and similar coleopteran pests.

Effects of cyproheptadine on the rat yolk sac membrane and embryonic development in vitro

Xenobiotica ◽  
1985 ◽  
Vol 15 (8-9) ◽  
pp. 695-699 ◽  
Author(s):  
B. P. Schmid ◽  
R. E. Hauser ◽  
P. Donatsch
Keyword(s):  
Embryonic Development ◽  
Yolk Sac ◽  
Development In Vitro

scholarly journals New Class of Small Nonpeptidyl Compounds BlocksPlasmodium falciparum Development In Vitro by Inhibiting Plasmepsins

2001 ◽  
Vol 45 (9) ◽  
pp. 2577-2584 ◽  
Author(s):  
Suping Jiang ◽  
Sean T. Prigge ◽  
Lan Wei ◽  
Yu-e Gao ◽  
Thomas H. Hudson ◽  
...  
Keyword(s):  
Cathepsin D ◽  
Mammalian Cells ◽  
Computational Docking ◽  
New Class ◽  
Automated Assay ◽  
Chemical Database ◽  
Plasmepsin Ii ◽  
Development In Vitro ◽  
Intraerythrocytic Stage

ABSTRACT Malarial parasites rely on aspartic proteases called plasmepsins to digest hemoglobin during the intraerythrocytic stage. Plasmepsins fromPlasmodium falciparum and Plasmodium vivax have been cloned and expressed for a variety of structural and enzymatic studies. Recombinant plasmepsins possess kinetic similarity to the native enzymes, indicating their suitability for target-based antimalarial drug development. We developed an automated assay of P. falciparum plasmepsin II andP. vivax plasmepsin to quickly screen compounds in the Walter Reed chemical database. A low-molecular-mass (346 Da) diphenylurea derivative (WR268961) was found to inhibit plasmepsins with a K i of 1 to 6 μM. This compound appears to be selective for plasmepsin, since it is a poor inhibitor of the human aspartic protease cathepsin D (K i greater than 280 μM). WR268961 inhibited the growth of P. falciparum strains W2 and D6, with 50% inhibitory concentrations ranging from 0.03 to 0.16 μg/ml, but was much less toxic to mammalian cells. The Walter Reed chemical database contains over 1,500 compounds with a diphenylurea core structure, 9 of which inhibit the plasmepsins, withK i values ranging from 0.05 to 0.68 μM. These nine compounds show specificity for the plasmepsins over human cathepsin D, but they are poor inhibitors of P. falciparum growth in vitro. Computational docking experiments indicate how diphenylurea compounds bind to the plasmepsin active site and inhibit the enzyme.

Abnormal Structure of von Willebrand Factor in Myeloproliferative Syndrome Is Associated to Either Thrombotic or Bleeding Diathesis

1987 ◽  
Vol 58 (02) ◽  
pp. 753-757 ◽  
Author(s):  
M F López-Fernández ◽  
C López-Berges ◽  
R Martín ◽  
A Pardo ◽  
F J Ramos ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Proteinase Inhibitors ◽  
Relative Proportion ◽  
Variable Degree ◽  
Bleeding Diathesis ◽  
Myeloproliferative Syndrome ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the “in vivo” proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities.The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring “in vivo” rather than “in vitro”, and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Influence of corticosteroids and thyroxine on lung development in vitro

1985 ◽  
Vol 110 (1_Suppla) ◽  
pp. S35-S36 ◽  
Author(s):  
B. ZIMMERMANN
Keyword(s):  
Lung Development ◽  
Development In Vitro

The effect of development in vitro

2014 ◽  
Author(s):  
Hitomi Obata ◽  
Maki Kamoshita ◽  
Tsubasa Kato ◽  
Junya Ito ◽  
Naomi Kashiwazaki
Keyword(s):  
Development In Vitro
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