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R H Zhang

Publications and source records attributed to R H Zhang.

27 records · Page 2Linked to original sources

Genistein is a natural inhibitor of hexose and dehydroascorbic acid transport through the glucose transporter, GLUT1.

Genistein is a dietary-derived plant product that inhibits the activity of protein-tyrosine kinases. We show here that it is a potent inhibitor of the mammalian facilitative hexose transporter GLUT1. In human HL-60 cells, which express GLUT1, genistein inhibited the transport of dehydroascorbic acid, deoxyglucose, and methylglucose in a dose-dependent manner. Transport was not affected by daidzein, an inactive genistein analog that does not inhibit protein-tyrosine kinase activity, or by the general protein kinase inhibitor staurosporine. Genistein inhibited the uptake of deoxyglucose and dehydroascorbic acid in Chinese hamster ovary (CHO) cells overexpressing GLUT1 in a similar dose-dependent manner. Genistein also inhibited the uptake of deoxyglucose in human erythrocytes indicating that its effect on glucose transporter function is cell-independent. The inhibitory action of genistein on transport was instantaneous, with no additional effect observed in cells preincubated with it for various periods of time. Genistein did not alter the uptake of leucine by HL-60 cells, indicating that its inhibitory effect was specific for the glucose transporters. The inhibitory effect of genistein was of the competitive type, with a Ki of approximately 12 microM for inhibition of the transport of both methylglucose and deoxyglucose. Binding studies showed that genistein inhibited glucose-displaceable binding of cytochalasin B to GLUT1 in erythrocyte ghosts in a competitive manner, with a Ki of 7 microM. These data indicate that genistein inhibits the transport of dehydroascorbic acid and hexoses by directly interacting with the hexose transporter GLUT1 and interfering with its transport activity, rather than as a consequence of its known ability to inhibit protein-tyrosine kinases. These observations indicate that some of the many effects of genistein on cellular physiology may be related to its ability to disrupt the normal cellular flux of substrates through GLUT1, a hexose transporter universally expressed in cells, and is responsible for the basal uptake of glucose.

Amino Acids↗

Resolution of the facilitated transport of dehydroascorbic acid from its intracellular accumulation as ascorbic acid.

We performed a detailed kinetic analysis of the uptake of dehydroascorbic acid by HL-60 cells under experimental conditions that enabled the differentiation of dehydroascorbic acid transport from the intracellular reduction/accumulation of ascorbic acid. Immunoblotting and immunolocalization experiments identified GLUT1 as the main glucose transporter expressed in the HL-60 cells. Kinetic analysis allowed the identification of a single functional activity involved in the transport of dehydroascorbic acid in the HL-60 cells. Transport was inhibited in a competitive manner by both 3-O-methyl-D-glucose and 2-deoxy-D-glucose. In turn, dehydroascorbic acid competitively inhibited the transport of both sugars. A second functional component identified in experiments measuring the accumulation of ascorbic acid appears to be associated with the intracellular reduction of dehydroascorbic acid to ascorbic acid and is not directly involved in the transport of dehydroascorbic acid via GLUT1. Transport of dehydroascorbic acid by HL-60 cells was independent of the presence of external Na+, whereas the intracellular accumulation of ascorbic acid was found to be a Na(+)-sensitive process. Thus, the transport of dehydroascorbic acid via glucose transporters is a Na(+)-independent process which is kinetically and biologically separable from the reduction of dehydroascorbic acid to ascorbic acid and its subsequent intracellular accumulation.

3-O-Methylglucose↗

Human HL-60 myeloid leukemia cells transport dehydroascorbic acid via the glucose transporters and accumulate reduced ascorbic acid.

The cellular accumulation of vitamin C, a substance critical to human physiology, is mediated by transporters located at the cell membrane, and is regulated in a cell-specific manner. Neoplastic cells may have special needs for vitamin C. Therefore, we investigated the transport of vitamin C in a human myeloid leukemia cell line (HL-60). The HL-60 cells lacked the capacity to transport the reduced form of vitamin C, ascorbic acid, but they showed a remarkable ability to transport the oxidized form of vitamin C, dehydroascorbic acid (DHA). Uptake-accumulation studies indicated that the HL-60 cells accumulated ascorbic acid when provided with DHA. Kinetic analysis showed the presence of two functional activities involved in the uptake of DHA, one with low affinity and one with high affinity. Cytochalasin B and phloretin, which inhibit the passage of glucose through the facilitative glucose transporters, also inhibited the transport of DHA by HL-60 cells. Transport of DHA was completed by D- but not L-hexoses, and was sensitive to D-hexose-dependent counter transport acceleration. These data support the concept that HL-60 myeloid leukemic cells transport DHA through the facilitative hexose transporters (glucose transporters) and accumulate the reduced form of ascorbic acid.

3-O-Methylglucose↗

[A summary on effects of combined acupuncture anaesthesia for critical, old, week, special patients].

This article summarized the effects of combined acupuncture-epidural anaesthesia (n = 37) and epidural anaesthesia (n = 37) for operations of patients being in a critical, old, weak or special condition. And, the effects were compared between the two different anaesthetic methods in a similar clinical condition. The patients studied were almost complicated with coronary arteriosclerotic heart disease, hypertension or other types of disease excepting the surgical condition. There were different degrees of functional disturbance in their important visceral organs. The states of the body were all belong to critical or weak condition. This might be a difficulty of considerably great for anaesthesia and operation. By using combined acupuncture-epidural anaesthesia, the advantages of acupuncture anaesthesia and epidural anaesthesia were brought into fully play, and, the defect of incomplete analgesia as well as inadequate muscle relaxation was remedied. By acupuncture for 30 to 40 minutes, the EGGs that were originally abnormal had shown some improvement in parts of case and recovered to normal in individual patient. Even though the EGGs had not shown improvement in some cases, but, took no further steps to deteriorate, although undergoing harmful effects in operative process, such as exploration, hemorrhage or others. In some cases, the circulative function showed stabilization exceeding one's expectations. The result showed that acupuncture has a regulative role on the cardiovascular system, thus enhancing the safety in anaesthetic process.

Abdomen↗

Hypotensive action of parathyroid hormone in chicken.

In a recent series of studies, the hypotensive action of parathyroid hormone (PTH) was demonstrated in several vertebrate species. In mammals, the mechanism of this direct action on specific vascular beds was studied. An increase in intracellular cyclic AMP and an inhibition of entry of extracellular calcium into the vascular tissue was correlated with the vasorelaxing action of PTH. In the present report, PTH was found to relax chicken mesenteric vessels in vitro in the presence or absence of constriction with concentrated potassium chloride (KCl). PTH produced dose-related inhibition of the chicken vessel constricted with 10, 20, 40, or 60 mM KCl. Extracellular calcium-dependent constriction of the chicken mesenteric artery was also decreased by PTH. An inhibitory effect was also observed with D600, a known calcium-entry inhibitor, in the above in vitro test systems. The low affinity lanthanum-resistant pool of calcium, which supposedly reflects the rate of calcium entry into cells, was also decreased by PTH in the control or KCl-stimulated chicken mesenteric artery. These data suggest that PTH may produce vasorelaxation in chicken mesenteric artery by inhibition of calcium entry into cells. This vessel from the chicken seems to have a high turnover rate of calcium and may be a good model for studying the effects of substances on calcium entry in vascular smooth muscle.

Animals↗