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Biomedical subjects

Y Ren

Publications and source records attributed to Y Ren.

At least 145 records · Page 8Linked to original sources

Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis.

We have investigated the cell surface recognition mechanisms used by human monocyte-derived macrophages (M phi) in phagocytosis of intact aging human neutrophils (PMNs) undergoing apoptosis. This study shows that the adhesive protein thrombospondin (TSP) was present in the interaction, both associated with the M phi surface and in solution at a mean concentration of 0.59 micrograms/ml. The interaction was inhibited by treatment of M phi (but not aged PMN) with cycloheximide, but could be "rescued" by replenishment with exogenous TSP. Under control conditions, M phi recognition of aged PMNs was specifically potentiated by purified platelet TSP at 5 micrograms/ml, present either in the interaction or if preincubated with either cell type, suggesting that TSP might act as a "molecular bridge" between the two cell types. In support, both aged PMN and M phi were found to adhere to TSP, and phagocytosis of aged PMN was specifically inhibited by (a) excess soluble TSP; (b) antibodies to TSP that also inhibit TSP-mediated adhesion to aged PMN; and (c) down-regulation of M phi receptors for TSP by plating M phi on TSP-coated surfaces. Furthermore, inhibition with mAbs/Arg-Gly-Asp-Ser peptide of the candidate M phi receptors for TSP, CD36, and alpha v beta 3 exerted synergistic effects on both M phi recognition of aged PMN and M phi adhesion to TSP, indicating that "two point" adhesion of TSP to these M phi structures is involved in phagocytosis of aged PMN. Our findings indicate newly defined roles for TSP and CD36 in phagocytic clearance of senescent neutrophils, which may limit inflammatory tissue injury and promote resolution.

Antibodies, Monoclonal↗

[Compatibility of Chinese drugs radix Aconiti carmichaeli with rhizoma Pinelliae].

To find out whether the Chinese drug Radix Aconiti Carmichaeli is compatible with another Chinese drug Rhizoma Pinelliae in preparation, the two medicinal herbs were made into different forms of decoctions. Experiments with these decoctions were carried out to observe the action on isolated hearts of toads and the ECG and acute toxicity on mice. The results showed that in terms of toxicity there was no marked increase in the mixed decoction as compared with the other two decoctions prepared from Radix Aconiti Carmichaeli and Rhizoma Pinelliae separately.

Animals↗

[Spermine inhibition of in vitro fertilizing ability of human spermatozoa and its possible mode of action].

The direct effect of spermine at various concentrations (0.25-8.0 mmol/L) on in vitro fertilizing ability of human spermatozoa was evaluated by the penetration test of zona-free hamster egg. To study the effect of spermine on capacitation, as judged by the rate of penetration, spermatozoa were incubated in BWW with various concentrations of spermine for 6 h at 37 degrees C. The hyperactivated motility of spermatozoa was markedly inhibited by spermine at a concentration of 4.0 mmol/L. The penetration rate was decreased proportionally to the dose of spermine used. Spermatozoa were incubated in BWW with 0.5 mmol/L spermine for 6 h and another 4 h after spermine was washed off with spermine-free BWW. The percentage of penetration was comparable to that of the control. Therefore, spermine-mediated inhibition of capacitation was reversible. Moreover, exogenous dbcAMP (0.5-1.0 mmol/L) or caffeine (10 mmol/L) could antagonize significantly the spermine-induced inhibition of capacitation with a correlation coefficient of 0.990. The content of spermine in fertile men spermatozoa was assayed by HPLC. Before capacitation spermine in spermatozoa was 7.05 micrograms/10(7) cells, whereas after capacitation it was no longer detectable, indicating that spermine may be an inhibitor of in vitro capacitation in human sperm. To study the effect of spermine on capacitated sperm, spermine was added to the BWW medium after sperm had been preincubated in spermine-free BWW. The persistent presence of spermine could interfere with spermatozoa attachment to, binding to and penetration into zona-free hamster eggs, which was related to the concentration (r = 0.820) used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prostaglandin H synthase: spectroscopic studies of the interaction with hydroperoxides and with indomethacin.

Prostaglandin H synthase has both a heme-dependent peroxidase activity and a cyclooxygenase activity. A current hypothesis considers the cyclooxygenase reaction to be a free radical chain reaction, initiated by an interaction of the synthase peroxidase with hydroperoxides leading to the production of a tyrosyl free radical [Stubbe, J. A. (1989) Annu. Rev. Biochem. 58, 257-285]. We have examined the kinetics of radical formation with both ethyl hydroperoxide (EtOOH) and 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and have analyzed the effects of indomethacin (a selective cyclooxygenase inhibitor) and tetranitromethane (TNM; a selective agent for nitration of tyrosyl residues) on the synthase. At -14 degrees C both EtOOH and 15-HPETE generated within 5 s a free radical species whose electron paramagnetic resonance spectrum was dominated by a doublet centered at g = 2.005 (splitting of approximately 16 G; overall peak-to-trough width of 35 G) that has been attributed to tyrosyl radical. The doublet subsequently gave way to a singlet with a similar peak-to-trough width; the doublet-to-singlet transition was complete in 20-60 s. The intensity of the doublet/singlet combination peaked at 0.6 spins/heme after 120 s with EtOOH and at about 0.3 spins/heme after 20 s with 15-HPETE; the radical intensity declined slowly with EtOOH but more rapidly with 15-HPETE. Reaction of the indomethacin-synthase complex with EtOOH resulted in a narrower (peak-to-trough width of 24 G) singlet free radical signal, with no evidence of an earlier doublet; the intensity of the singlet peaked at 0.45 spins/heme after about 300 s. Reaction of TNM-treated synthase with EtOOH resulted in a singlet almost identical with that seen for the indomethacin-synthase complex. Reaction of the synthase holoenzyme with TNM at pH 8.0 led to inactivation of both cyclooxygenase and peroxidase activity, with the former being lost rapidly and completely while the latter was lost slowly and to about 50%. Ibuprofen, a competitive cyclooxygenase inhibitor, slowed the rate of inactivation of the cyclooxygenase by about 20-fold. The rate of inactivation of the cyclooxygenase activity in synthase apoenzyme by TNM was also about 20-fold less than that observed with the holoenzyme. Amino acid analyses revealed that TNM-reacted holoenzyme with less than 10% residual activity contained 1.8 nitrotyrosines/subunit; apoenzyme reacted under the same conditions had greater than 80% of the original activity and contained 0.7 nitrotyrosine/subunit.(ABSTRACT TRUNCATED AT 400 WORDS)

Cyclooxygenase Inhibitors↗