ABSTRACT
The prostate gland of humans and other animals accumulates a level of zinc that is 3-10 times greater than that found in other tissues. Associated with this ability to accumulate zinc is a rapid zinc uptake process in human prostate cells, which we previously identified as the hZIP1 zinc transporter. We now provide additional evidence that hZIP1 is an important operational transporter that allows for the transport and accumulation of zinc. The studies reveal that hZIP1 (SLC39A1) but not hZIP2 (SLC39A2) is expressed in the zinc-accumulating human prostate cell lines, LNCaP and PC-3. Transfected PC-3 cells that overexpress hZIP1 exhibit increased uptake and accumulation of zinc. The V(max) for zinc uptake was increased with no change in K(m). Along with the increased intracellular accumulation of zinc, the overexpression of hZIP1 also results in the inhibition of growth of PC-3 cells. Down-regulation of hZIP1 by treatment of PC-3 cells with hZIP1 antisense oligonucleotide resulted in a decreased zinc uptake. Uptake of zinc from zinc chelated with citrate was as rapid as from free zinc ions; however, the cells did not take up zinc chelated with EDTA. The cellular uptake of zinc is not dependent upon an available pool of free Zn(2+) ions. Instead, the mechanism of transport appears to involve the transport of zinc from low molecular weight ligands that exist in circulation as relatively loosely bound complexes with zinc.
Subject(s)
Carrier Proteins/metabolism , Prostate/cytology , Zinc/metabolism , Carrier Proteins/genetics , Cation Transport Proteins , Cell Division , Cell Line , Chelating Agents/pharmacology , Humans , Kinetics , Ligands , Male , Prostate/metabolism , Transfection , Zinc Radioisotopes/pharmacokineticsABSTRACT
The effect of chloroquine phosphate on plasma nicotinic acid levels in adult male albino rats was investigated. Pyrogen free chloroquine phosphate in physiological saline was administered subcutaneously to rats in a dose of 15 mg/kg body weight daily for eleven succeeding days in the treatment group. A control group was given equal volume of physiological saline daily for eleven succeeding days. Nicotinic acid concentration in the plasma was determined [1] Plasma nicotinic acid level was found to be significantly reduced (P < 0.01) throughout the duration of treatment. No change was observed in the control group. The significant reduction of plasma nicotinic acid level observed in this study may not be unrelated to competitive inhibition of the enzyme tryptophan dioxygenase by chloroquine phosphate.
Subject(s)
Antimalarials/adverse effects , Chloroquine/analogs & derivatives , Chloroquine/adverse effects , Niacin/blood , Animals , Biotransformation , Drug Evaluation, Preclinical , Drug Monitoring , Male , Rats , Rats, Inbred Strains , Tryptophan/metabolism , Tryptophan Oxygenase/antagonists & inhibitorsABSTRACT
The effect of incubation of coupled liver mitochondria on varying concentration of zinc ion was determined. A low concentration of 6 microM zinc ion was found to inhibit the rate of oxygen consumption of the liver mitochondria significantly [P < 0.01]. There was uncoupling of the liver mitochondria when subjected to varying incubation periods. There was no change observed in the control experiment. Zinc-citrate inhibited the rate of oxygen consumption significantly [P < 0.01] when compare with the control. The changes observed in the Zn-aspartate were insignificant. Zn-EDTA had no inhibitory or stimulatory effect on the rate of liver mitochondrial oxygen consumption.
Subject(s)
Mitochondria, Liver/metabolism , Oxygen Consumption/drug effects , Zinc/pharmacology , Animals , In Vitro Techniques , Male , Rats , Rats, Wistar , Time FactorsABSTRACT
The inhibitory effect of extracellular zinc ion on the rate of oxygen consumption of rat brain mitochondria pre-incubated in 1.0 mMol Ca(2+)EDTA were determined. There was a significant increase [P < 0.01] in the rate of oxygen consumption in the rat brain mitochondria pre-incubated in 1.0 mMol Ca(2+)EDTA in a succinate initiated reaction. The reverse was the case when the concentration of Ca(2+)EDTA was increased to 10 mMol. A 20 microMol zinc-aspartate was found to have no inhibitory effect on the rate of oxygen consumption of the brain mitochondria pre-incubated with 1.0 mMol Ca(2+)EDTA when compared with the control that lacked 1.0 mMol Ca(2+)EDTA, however there was a significant decrease [P < 0.01] in the rate of oxygen consumption of the rat brain mitochondria in the control experiment.
Subject(s)
Brain/metabolism , Mitochondria/drug effects , Oxygen Consumption/drug effects , Zinc/pharmacology , Animals , Edetic Acid/pharmacology , Male , Mitochondria/metabolism , Rats , Rats, Wistar , Succinic Acid/metabolismABSTRACT
This study was undertaken to determine the effects of zinc sulphate on the weights of pregnant rats, on the food and water consumption during gestation, litters weight at birth, the number of litters at birth and the accumulation of zinc in selected organs of the litters. Zinc sulphate in the dose of 1 mg/l and 20 mg/l drinking water was administered to both pregnant and non-pregnant for the period of gestation. The results indicated a significant [P < 0.005] increase in body weights of pregnant rats when compared with the corresponding controls (non-pregnant and zinc free rats). The values of food consumption in the pregnant rats during 1st, 2nd and 3rd week were significantly [P < 0.05] higher than the value obtained for the non-pregnant and the control of non-pregnant rats. Pregnant rats administered with 20 mg/l of zinc drinking water showed a sharp decline in the food consumption from the 3rd week and this was continuous till the end of gestation. The quantity of water consumed by pregnant rats was significantly [P < 0.005] higher than the control group (zinc free non-pregnant rats). Non-pregnant rats that received 1 mg/l of zinc drinking water significantly [P < 0.05] consumed more water than those that received 20 mg/l zinc drinking water. There was no significant difference between maternal weights of the experimental and control rats at parturition. Rats administered with 1 mg/l zinc delivered the biggest litters-size, which was significantly [P < 0.05] different from either those administered with 20 mg/l of zinc drinking water or zinc free water respectively. The weights of the liver, thyroid, and pancreas from the litters were significantly [P < 0.05] higher than those from the control rats. The liver was found to accumulate significant [P < 0.05] higher concentration of zinc when compared with the control group.
Subject(s)
Body Weight/drug effects , Eating/drug effects , Litter Size/drug effects , Zinc/pharmacology , Animals , Animals, Newborn , Birth Weight/drug effects , Dose-Response Relationship, Drug , Drinking/drug effects , Female , Liver/drug effects , Liver/growth & development , Liver/metabolism , Organ Size/drug effects , Pancreas/drug effects , Pancreas/growth & development , Pregnancy , Rats , Rats, Wistar , Thyroid Gland/drug effects , Thyroid Gland/growth & development , Time Factors , Zinc/pharmacokineticsABSTRACT
The effect of starvation on liver weight and the specific activity of hepatic tryptophan dioxygenase (EC 1.13.1.12) in prepubertal male rats (Vom Ife strain) maintained in several stages of fasting was studied. The specific activity of hepatic tryptophan dioxygenase was significant after 24 h of fasting. It then fell to a nadir at 96 h before a secondary but significant peak after 120 h. During refeeding after a 120 h fast the specific activity was initially lower than controls after 96 h. The liver weight was significantly lower than controls throughout the fasting period although it was higher at 96 h. On refeeding the liver weight attained control values after 96 h. There appears to be some adaptive change with respect to liver weight and the specific activity of tryptophan dioxygenase at 96 h during fasting, and on refeeding after a severe fast.
Subject(s)
Fasting/physiology , Liver/anatomy & histology , Tryptophan Oxygenase/metabolism , Animals , Fasting/metabolism , Gluconeogenesis/physiology , Indoleamine-Pyrrole 2,3,-Dioxygenase , Liver/enzymology , Male , Organ Size/physiology , RatsABSTRACT
The effects of testosterone on mitochondrial aspartate aminotransferase (mAAT) synthesis in rat ventral prostate was investigated. Procedures for the isolation, purification and characterization of AAT isozymes were developed and described. Purified mAAT preparations contained no demonstrable contaminating proteins. Prostatic mAAT was characterized as a cationic protein with an estimated mol. wt of 120,000. Cytoplasmic AAT (cAAT) isozyme was identified as an anionic protein with an estimated mol. wt of 132,000. A cytosolic cationic isozyme, similar to mAAT, was also identified as pre-mAAT. Testosterone administration to castrated rats resulted in significant increases in leucine incorporation into mAAT, in the level of mAAT, and in mAAT activity. These effects of testosterone were observed within 2 h of administration. Conversely, testosterone administration had none of these effects on cAAT or on non-AAT protein pool. Testosterone treatment did appear to increase leucine incorporation into pre-mAAT. Testosterone treatment in organ cultures and in prostate epithelial cell cultures resulted in the same stimulatory effects on mAAT as observed in the in vivo studies. The hormone was effective at the physiological concentration of 2 X 10(-9) M. These results indicated that testosterone has a rapid and specific effect on the biosynthesis of mAAT. This continues to support our proposal that testosterone regulates prostate citrate production via a stimulatory effect on mAAT which results in increased mitochondrial synthesis of citrate from aspartate.