Disease relevance of cis-4-Hydroxy-L-proline

• Prevention of collagen deposition following pulmonary oxygen toxicity in the rat by cis-4-hydroxy-L-proline [1].
• Both CHP and A2C were completely inactive against the 450.1 mammary tumor and the EHS sarcoma [2].
• Injections of cHyp in liposomes every 5 days partially prevented hypertension and vascular collagen accumulation during a 3-week exposure to hypoxia, and the dose required was one tenth the dose of unencapsulated cHyp [3].
• We conclude that cHyp encapsulated in liposomes prevents bleomycin-induced fibrosis by biochemical measurements [4].
• We studied whether the therapeutic efficacy of the antifibrotic agent cis-4-hydroxy-L-proline (cHyp) in preventing bleomycin-induced pulmonary fibrosis in rats is enhanced by intratracheal delivery in liposomes [4].

High impact information on cis-4-Hydroxy-L-proline

• Fibroblasts freshly isolated from embryonic tendons were incubated with a proline analog, cis-4-hydroxy-L-proline, which is incorporated into protein and which leads to the intracellular accumulation of nonhelical procollagen [5].
• Of the proline analogues tested against 450.1 tumor cells, A2C and CHP were the most potent inhibitors of cell growth [2].
• In culture, CHP specifically inhibited those tumor cells that synthesized basement-membrane collagen [2].
• Against CD8F1 mammary tumors, treatment with maximum tolerated doses of CHP and A2C resulted in a slight but insignificant inhibition of tumor growth [2].
• Proline analogues such as cis-4-hydroxy-L-proline (CHP) and L-azetidine-2-carboxylic acid (A2C) were tested for their antitumor activity in tissue culture and in vivo [2].

Chemical compound and disease context of cis-4-Hydroxy-L-proline

• Animals were injected with cHyp, 200 mg/kg body weight, or BAPN, 150 mg/kg body weight, twice daily for 3 months [6].
• We investigated whether excess vascular collagen contributes to chronic hypoxic pulmonary hypertension by administering the proline analogue cis-4-hydroxy-L-proline (cHyp), an agent relatively specific for inhibiting collagen production, to rats exposed to chronic hypoxia [7].

Biological context of cis-4-Hydroxy-L-proline

• Right ventricular pressure was 11 +/- 1 mm Hg (mean +/- SEM) 5 days after a single intravenous injection of 200 mg/kg cHyp in liposomes compared with 14 +/- 1 mm Hg in rats injected with empty liposomes; hydroxyproline content was also reduced by cHyp treatment (87 +/- 6 versus 107 +/- 7 micrograms per vessel) (p less than 0.05 for both, n = 6-9) [3].
• Effects of cis-4-hydroxy-L-proline, and inhibitor of Schwann cell differentiation, on the secretion of collagenous and noncollagenous proteins by Schwann cells [8].
• We have shown that administration of the antifibrotic agent cis-4-hydroxy-L-proline (cHyp) to rats at the onset of exposure to hypoxia prevents collagen accumulation in pulmonary arteries and the rise in pulmonary blood pressure [9].
• Lungs from day 15 gestation were incubated for 4 days in (1) the control medium (Dulbecco's Modified Eagle Medium + 10% Fetal Bovine Serum) alone (control), (2) control medium plus 2 mM beta-D-xyloside (beta-XYL), (3) control medium plus 2 mM alpha-D-xyloside (alpha-XYL), (4) control medium plus 50 micrograms/mL cis-4-hydroxy-L-proline (cis-HYP) [10].
• There was no effect of cHyp on cardiac output [7].

Anatomical context of cis-4-Hydroxy-L-proline

• Therapeutic doses of cHyp in liposomes injected for 6 months affected tensile properties of main pulmonary artery and aorta, but there were no apparent histological effects on other organs [3].
• The prolonged effect of a single injection of cHyp in liposomes may be due to uptake of the liposomes by the endothelium [3].
• A new class of nontransformed revertant cells has been isolated from the ras-transformed cell line DT using cis-4-hydroxy-L-proline (CHP) as a selective agent [11].
• The effect of cis-4-hydroxy-L-proline on intracellular degradation of newly synthesized collagen by freshly isolated chick tendon fibroblasts [12].
• In the present report we demonstrate that the proline analog, cis-4-hydroxy-L-proline, will inhibit myotube formation in vitro without affecting the aggregation of cells (fusion?) [13].

Associations of cis-4-Hydroxy-L-proline with other chemical compounds

• Effects of cis-4-hydroxy-L-proline on the androgen-induced growth of the lateral prostate of the prepubertally castrated guinea pig [14].
• Effect of cis-4-hydroxy-L-proline on lung mechanics and collagen content of bleomycin-treated hamsters [15].
• However, incubation of type II cells with alpha,alpha'-dipyridyl or cis-4-hydroxy-L-proline, agents which disrupt triple-helix formation within collagenous peptide domains, inhibited sialylation, intracellular transport to the lamellar body fraction and secretion [16].
• NMR studies have been used to examine conformational effects in thyrotropin-releasing hormone (TRH), the epimer incorporating D-His, and their analogues where trans- and cis-4-hydroxy-L-proline replace L-proline (Pro) [17].

Gene context of cis-4-Hydroxy-L-proline

• Isolation of a new class of 'flat' revertants from ras-transformed NIH3T3 cells using cis-4-hydroxy-L-proline [11].
• Hypoxia increased elastin from 1.1 +/- 0.1 to 2.4 +/- 0.2 mg/artery (p less than 0.05); cHyp had no apparent effect since elastin was 2.1 +/- 0.1 mg/artery [7].

References