Effect of the proline analogue azetidine-2-carboxylic acid on collagen synthesis in vivo I. Arrest of collagen accumulation in growing chick embryos

1971 ◽  
Vol 236 (3) ◽  
pp. 517-527 ◽  
Author(s):  
Joseph M. Lane ◽  
Peter Dehm ◽  
Darwin J. Prockop
1965 ◽  
Vol 25 (1) ◽  
pp. 69-78 ◽  
Author(s):  
John R. Coleman ◽  
Heinz Herrmann ◽  
Barbara Bess

The relationship between the rates of increase of corneal protein fractions and incorporation of labeled precursors has been examined during embryonic and early posthatching development of the chick corneal stroma. Non-collagen protein increased gradually from 9 through 20 days of incubation. Collagen accumulated approximately logarithmically through the 19th day, the most rapid rate occurring between 13 and 20 days of incubation. The rates at which labeled amino acids are incorporated into collagen in vivo and in vitro undergo marked changes during the last week of embryonic development, corresponding closely to the rate of collagen accumulation in vivo; whereas incorporation into non-collagen protein changes much less markedly. Changes in the rate of incorporation of precursors into collagen are not due to changes in the rate of conversion of collagen from the soluble to insoluble form, or to changes in the endogenous amino acid pool size. Chick embryo corneal stroma collagen turns over very slowly, if at all. Non-collagen protein turns over more rapidly. An increase in cell number, as indicated by DNA content, does not account for the increased rate of collagen synthesis between the 9th and 16th day of incubation. It is concluded that the observed changes in collagen synthesis reflect changing activities in the individual cornea fibroblasts. These activities are comparable in the intact tissue in vivo and in isolated corneas in vitro.


2018 ◽  
Author(s):  
Joan Chang ◽  
Richa Garva ◽  
Adam Pickard ◽  
Ching-Yan Chloé Yeung ◽  
Venkatesh Mallikarjun ◽  
...  

Collagen is the most abundant secreted protein in vertebrates that persists throughout life without renewal. The unchanging nature of collagen contrasts with observed continued collagen synthesis throughout adulthood and with conventional transcriptional and translational homeostatic mechanisms that replace damaged proteins with new copies. Here we show circadian clock regulation of procollagen transport from ER-to-Golgi and Golgi-to-plasma membrane by sequential rhythmic expression of SEC61, TANGO1, PDE4D and VPS33B. The result is nocturnal procollagen synthesis and daytime collagen fibril assembly in mice. Rhythmic collagen degradation by CTSK maintains collagen homeostasis. This circadian cycle of collagen synthesis, assembly and degradation affects only a pool of newly-synthesized collagen whilst maintaining the persistent collagen network. Disabling the circadian clock causes collagen accumulation and abnormal fibrils in vivo. In conclusion, our study has identified a circadian clock mechanism of protein homeostasis in which a sacrificial pool of collagen is synthesized and removed to maintain tissue function.


Author(s):  
M.J.C. Hendrix ◽  
D.E. Morse

Atrial septal defects are considered the most common congenital cardiac anomaly occurring in humans. In studying the normal sequential development of the atrial septum, chick embryos of the White Leghorn strain were prepared for scanning electron microscopy and the results were then extrapolated to the human heart. One-hundred-eighty chick embryos from 2 to 21 days of age were removed from their shells and immersed in cold cacodylate-buffered aldehyde fixative . Twenty-four embryos through the first week post-hatching were perfused in vivo using cold cacodylate-buffered aldehyde fixative with procaine hydrochloride. The hearts were immediately dissected free and remained in the fixative a minimum of 2 hours. In most cases, the lateral atrial walls were removed during this period. The tissues were then dehydrated using a series of ascending grades of ethanol; final dehydration of the tissues was achieved via the critical point drying method followed by sputter-coating with goldpalladium.


2008 ◽  
Vol 95 (3) ◽  
pp. 530-535 ◽  
Author(s):  
I. CHOI ◽  
H.-S. KANG ◽  
Y. YANG ◽  
K.-H. PYUN

2021 ◽  
Vol 17 ◽  
Author(s):  
Peter Amir Halim ◽  
Hala Bakr El-Nassan ◽  
Yara Sayed El-Dash

Background: The reported binding mode of ibuprofen in the COX-2 binding site indicated that the carboxylic group binds with Arg-120 and Tyr-355 at the entrance of the cyclooxygenase channel and does not extend into the pocket. This accounted for the non-selectivity of ibuprofen. Based on this fact, we assumed that extending the length of the carboxylic acid moiety in ibuprofen and adding more bulky rigid groups as well as bulky groups carrying H-bonding functions might increase the selectivity and reduce the side effects of ibuprofen while maintaining its analgesic and anti-inflammatory activities. Objective: In this work, four series of ibuprofen derivatives were designed and prepared. The compounds were designed by increasing the length of the carboxylate group along with the incorporation of large hydrophobic groups. Method: Four series of ibuprofen derivatives were synthesized starting from ibuprofen. Their chemical structure was confirmed by spectral data. All the compounds were tested for their COX inhibitory activity. Results : The best COX-2 activity and selectivity were obtained with compounds 5c and 5d, which were subjected to further in vivo testing (carrageenan-induced paw edema, rat serum PGE2, TNF- α and IL-6, hot plate latency test) to investigate their anti-inflammatory and analgesic activities as well as their effects on the gastric mucosa. The anti-inflammatory activity of both compounds was comparable to that of ibuprofen, diclofenac, and indomethacin. Both compounds suppressed the production of PGE2 as well as the rat serum concentrations of both TNF-α and IL-6. This potent anti-inflammatory and analgesic behavior was not accompanied by any effect on the gastric mucosa. Docking simulation studies of the two compounds explained the higher selectivity for the COX-2 enzyme. Conclusion: Potent and selective ibuprofen derivatives can be successively obtained by extending the length of the carboxylic acid moiety in ibuprofen and adding more bulky rigid groups as well as bulky groups with H-bonding functions.


1981 ◽  
Vol 200 (2) ◽  
pp. 435-440 ◽  
Author(s):  
T Videman ◽  
I Eronen ◽  
T Candolin

Proline metabolism in vivo was studied during the development of immobilization osteoarthritis in rabbits. Collagen content was measured as the hydroxyproline concentration of the tissue in question. The incorporation of [3H]proline was used as the indicator for total protein synthesis; collagen synthesis rate was estimated from measurements of the specific radioactivity of hydroxyproline. Cartilage samples from knee and hip joints were analysed after 3, 7, 11, 18, 35 and 56 days of immobilization. The total protein and collagen synthesis rates of the immobilized legs increased and reached a maximum after 11-35 days. Although they decreased thereafter, these rates remained elevated to the end of the experiment. A slight increase in the synthetic activity of the non-immobilized contralateral legs was also detected after 7--18 days of immobilization. The isotope incorporation was markedly higher in tibial marginal tissue than in weight-bearing cartilage. In spite of the increased synthesis, no clear changes were found in the collagen content of the tissues studied during the experiment.


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