Disease relevance of NSC 49883

• Characteristics of the enzyme were compared with those of a gamma-glutamyl kinase partially purified from a 3,4-dehydroproline-sensitive E. coli [1].
• Effect of dehydroproline as a collagen synthetic inhibitor in paraquat-induced pulmonary fibrosis in beagle dogs [2].

High impact information on NSC 49883

• Flow cytometry revealed that expression of beta1 integrins, through which SMCs interact with collagen, was unaffected by EDHB or DHP [3].
• Here, we demonstrate that collagenase-3 mRNA expression in differentiating MC3T3-E1 cells is dependent upon the presence of ascorbic acid, is inhibited in the presence of the collagen synthesis inhibitor, 3,4-dehydroproline, and is stimulated by growth on collagen in the absence of ascorbic acid [4].
• Addition of the hydroxylation inhibitor, 3,4-dehydroproline, caused marked inhibition of collagen secretion as well as accumulation of underhydroxylated collagens within the cells [5].
• A specific inhibitor of collagen synthesis, 3,4-dehydroproline, blocked AA-dependent induction of promoter activity, indicating that regulation of the osteocalcin gene requires collagen matrix synthesis [6].
• Treating normal human osteoblasts with the proline analogue 3,4-dehydroproline, which destabilizes collagen triple helix formation and alters collagen synthesis, secretion, and turnover, also decreased microM [7].

Biological context of NSC 49883

• 3,4-Dehydroproline inhibits cell wall assembly and cell division in tobacco protoplasts [8].
• These mutants were selected using two phenotypes: the ability to degrade a toxic proline analogue, dehydroproline, due to overexpression of putA enzyme activity, or overexpression of lacZ from put::Mud operon fusions [9].
• Detailed methods are described for preparation of [3H]MeTRH by reduction of the dehydroproline precursor and its purification by ion exchange and antibody affinity chromatography [10].
• The unexpected increase in in vitro potency, oral bioavailability, and in vivo activity of inhibitors with dehydroproline as P2-isostere is discussed [11].

Anatomical context of NSC 49883

• Prolyl hydroxylase activity was partially inhibited in cells cultured with dehydroproline for 24 h, resulting in the synthesis of collagen in which the proline was underhydroxylated [12].
• Results for cultures treated with 3,4-dehydroproline suggested that ascorbate-induced production of extracellular matrix was important for maximal BMP-2 response in canine MSCs [13].
• The increase in bile duct collagen in proline-infused animals and in worm-implanted animals could be completely inhibited to the amount in controls by 3,4-dehydroproline [14].
• Guinea pig peritoneal macrophages were cultured for 24 h in the presence of two inhibitors of the biosynthesis of collagen-like molecules such as C1q : 10(-3) M 3,4-dehydroproline or 10(-4) M 2,2'-dipyridyl [15].
• When dehydroproline was added in vitro to membrane bound polysomes, the synthesis of collagenous proteins was preferentially inhibited [16].

Associations of NSC 49883 with other chemical compounds

• The hydroxylation inhibitor alpha, alpha'-dipyridyl, and triple-helix inhibitors cis-hydroxyproline and 3,4 dehydroproline had minimal effects on the buildup of polysome-associated pro al chains [17].

Gene context of NSC 49883

• 3,4-Dehydroproline also inhibited the induction of alkaline phosphatase and osteocalcin mRNAs [18].
• Mutation pro-220::Tn5, which increases the resistance of Escherichia coli to 3,4-dehydroproline (M. E. Stalmach, S. Grothe, and J. M. Wood, J. Bacteriol. 156:481-486, 1983), is not linked to putP, proP, or proU [19].
• A similar study on tropoelastin polypeptides extracted in their hydroxylated and under-hydroxylated forms from artery cells incubated with [3H]valine in the absence and presence of alpha alpha'-bipyridine or 3,4-dehydroproline confirmed this close relationship and suggested that tropoelastins a and b are likely to be the products of a single gene [20].
• 3,4-Dehydroproline-resistant mutants derived from a putP putA mutant lack proline porter II [21].
• Although P5C reductase did not act on proline, it also catalyzed the oxidation of 3,4-dehydroproline [22].

Analytical, diagnostic and therapeutic context of NSC 49883

• The addition of dehydroproline to mammalian cell cultures caused a marked reduction in prolyl hydroxylase activity [16].

References