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Biomedical subjects

K R Hightower

Publications and source records attributed to K R Hightower.

At least 37 records · Page 2Linked to original sources
PubMed1985

Cytotoxic effects of internal calcium on lens physiology: a review.

While calcium is possibly involved in cataractogenesis, it is unquestionably involved in normal lens physiology. Numerous reports have documented the many cellular processes in other tissues affected by alterations in cellular levels of calcium. The homeostasis of the lens is no less dependent on the critical balance of intracellular calcium. With advances being made in calcium-sensitive microelectrodes and pioneering studies progressing in ion channel electrophysiology, interest in calcium metabolism in the lens has been intensified. This report is an attempt to review recent findings that deal solely with biochemical changes resulting from calcium imbalances in the lens interior.

Animals↗
PubMed1985

The importance of membrane sulfhydryl groups to calcium homeostasis in the lens.

This study focused on whether changes in lens levels of glutathione and calcium, early events associated with cataract formation, were related or that one might cause the other. The first part of the investigation was concerned with the extent to which an increase in levels of intracellular calcium might alter GSH levels in lens fiber and epithelial cells. The results demonstrate that calcium accumulation, either at 19 degrees C or 37 degrees C, did not diminish the concentration of GSH. More importantly, GSH levels did not decline in opaque regions of a calcium-loaded lens. The reciprocal part of the problem focused on whether a decline in lens thiol might lead to an increase in levels of calcium and subsequent opacification. In particular, it was shown that treatment of lenses with parachloromercuribenzene sulphonic acid (PCMBS), a nonpenetrating sulphydryl probe, resulted in a 10-30% loss of membrane SH groups in the epithelium. Diminished numbers of SH groups was accompanied by chloride fluxes and an increase in membrane permeability to sodium and calcium with an influx of sodium and calcium leading to opacities. It is important to note that these changes occurred in the absence of any change in cellular levels of soluble protein-SH or GSH. Additional experiments suggest that calcium transport was not impaired, as evidenced by lack of inhibition of Ca-ATPase activity in lenses treated with PCMBS. The results suggest that one explanation for opacification is that oxidative insults, which diminish GSH levels, leads to a loss of important membrane SH groups.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Chloromercuribenzenesulfonate↗
PubMed1984

Calcium-induced high molecular weight proteins in the intact rabbit lens.

We have investigated the ability of Ca2+ to induce the formation of high molecular weight (HMW) proteins in the intact lens. Ca2+ cataracts were produced in rabbit lenses by culturing the lenses for either four days in medium containing 20 mM Ca2+ or for three days in medium containing 100 mM Ca2+. Lenses cultured in 20 and 100 mM Ca2+ medium became opaque after 20 hr and contained 30 and 200 times higher levels of Ca2+, respectively, than transparent lenses cultured in medium containing 1 mM Ca2+. Lenses exposed to 100 mM Mg2+ did not lose transparency. The opacification of the lenses extended to a depth of 1 mm into the cortical layer and did not involve the nucleus. No significant differences were found in the concentrations of either soluble or insoluble proteins present in freshly excised lenses and Ca2+ cataracts. Soluble HMW proteins, greater than 1.5 X 10(6) daltons, were in two- and five-fold greater amounts in the 20 and 100 mM Ca2+ cataracts, respectively, compared to controls. HMW protein present in the 100 mM Ca2+ cataract amounted to approximately 3% of the total soluble protein in the lens. The amount of Ca2+ present in the HMW fraction was 1 Ca2+ per 5 X 10(5) daltons, no higher than that present in the unaggregated crystallins. No evidence was found for covalent bonding in the aggregate. Results of polyacrylamide gel electrophoresis and double immunodiffusion indicated the presence of alpha- and beta- but not gamma-crystallin in the HMW protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Development and reversal of calcium-induced opacities in vitro.

An investigation into the role of calcium in the opacification process has focused on the relationship between the rate of opacification and the increase in the concentration of lens calcium. A laser scanning system was designed to monitor continuously transmitted light in opaque lenses, thereby permitting a correlation between calcium concentrations and the onset and development of opacification to be obtained. Lens opacification depended both on the magnitude of the increase in the concentration of lens calcium and the time during which calcium levels were raised. Relatively small increases in the content of lens calcium over culture periods of 20 hr were as effective in producing opacities as large increases in lens calcium levels over several hours. Reversal of lens opacities also depended on the concentration of lens calcium as well as the duration over which lenses were exposed to calcium.

Animals↗
PubMed1983

Changes in the distribution of lens calcium during development of x-ray cataract.

The present study was designed to examine the possible role of calcium in the opacification of x-ray-induced cataract in rabbit. The results demonstrate that the concentration of calcium in x-rayed lenses, just prior to lens hydration (7.5 weeks postirradiation), was twice that present in contralateral control lenses. At this stage of immature cataract, the lens nucleus remained transparent and maintained a normal level of calcium, but the lens cortex, containing regions of subcapsular opacification, accumulated a level of calcium that was twice that of the control. In the completely opaque mature cataract, (8-9 weeks postx-ray), both the cortex and nucleus had gained significant amounts of calcium. As the concentration of total calcium increased in the immature x-ray cataract, the amount of the cation bound to membranes and insoluble proteins of the cytosol also increased comparably. However, the relative proportion of calcium in the various fractions remained unaltered in the immature cataract; in both control lenses and immature cataracts, 20% of the total calcium remained in the membrane pellet and 70% was located in the soluble protein fraction. Only in the mature stage of cataract was a shift in the distribution of calcium apparent, as the proportion of calcium in the soluble protein fraction increased to 90%. Although only 7% of the total calcium in a mature cataract was bound to membrane, the amount represented a fivefold increase over the control. The results of this study demonstrate that an elevation in lens calcium accompanies the opacification process in x-ray cataract. The work also suggests that changes in calcium levels are not likely to result from inactivation of Ca-ATPase.

Animals↗
PubMed1983

The influence of calcium on protein synthesis in the rabbit lens.

Biosynthesis of lens proteins, as assessed by the incorporation of 14C-histidine, was investigated in young rabbit lenses cultured under conditions designed to specifically elevate lens calcium. While such lenses rarely were obtained without small degrees of Na/K imbalances, experiments with ouabain-treated lenses over comparable times indicated that changes solely in Na/K levels did not alter synthesis of lens crystallins. On the other hand, with far smaller changes in Na/K levels, excess calcium accumulation obtained by exposing lenses to A23187 or high levels of medium calcium invariably led to diminished synthesis of lens proteins. An increase in lens calcium from 0.2 mM to 0.6 mM led to a small but statistically insignificant decline in protein synthesis, while an increase to 1.4 mM or 1.9 mM resulted in a decline to values 50% and 11%, respectively, of the control. The results indicate that calcium may be important in influencing protein synthesis in the lens.

Animals↗
PubMed1983

Lens membrane damage associated with cryoextraction.

The effects of cryoextraction on transport characteristics of rabbit lenses were evaluated by measuring Na+ and Ca++ levels, initial rates of 86Rb accumulation, and bioelectric potentials. The results demonstrate that membrane damage results from cryoextraction and is partially reversible during subsequent culture. While the decline in potential often exceeds 30 mV, maximum recovery of 80% occurs during a 1-hour incubation in TC199 at 37 C. Changes in the integrity of the membranes also are indicated by the finding that rates of 86Rb accumulation in cryoextracted lenses are approximately 44% less than the rates found in control lenses after a 20-hour culture in TC199. The degree of damage incurred by lens membranes also is reflected by a 10% increase in Na+ and 20% increase in Ca++ levels during 3 hours of culture. After extended culture periods, further increases in the concentration of Na+ (40%) and Ca++ (120%) were found to occur. Brief exposure of cryoextracted rabbit lenses to physiologic saline in a manner similar to that employed for photographic documentation of cataracts resulted in a marked decline in potential, 86Rb uptake, and an increase in Na and Ca content. In contrast, saline had little or no effect on these parameters in lenses excised by cutting the zonules. The results suggest that the observed decline in 86Rb accumulation in a limited number of cryoextracted cortico-nuclear cataracts compared with clear eye bank lenses may be attributed, in part, to damage to lens membranes by cryoextraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1982

Ca++-induced cataract.

Cataracts in cultured rabbit lenses were produced by elevation of internal calcium. Experimental procedures were successful in increasing levels of total and bound Ca++, often without significant changes in sodium, potassium, or water content. Although the excess in calcium was predominantly associated with water-soluble proteins and was freely diffusible, a significant amount was bound to membranes and cytosol water-insoluble proteins. Thus, in lenses with a 10-fold increase in total Ca++, the bound Ca++ increased twofold, nearly 35% of which remained fixed to water-insoluble and membrane proteins after exhaustive (72 hr) dialysis. In contrast, over 95% of the Ca++ in water-soluble protein fractions was removed by dialysis.

Animals↗
PubMed1981

Metabolic studies on calcium transport in mammalian lens.

Three important findings concerning the calcium pump in a mammalian lens are reported: 1) glycolysis is sufficient to support active transport of calcium in the young rabbit lens; 2) in addition to the epithelium posterior and anterior fibers are involved in calcium transport; 3) inhibition of glycolysis and the calcium pump result in calcium accumulation and subsequent opacification. That respiration does not contribute to the energy needs of the Ca++ pump is based on results which demonstrate that cyanide, dinitrophenol, and azide have no effect on 45Ca efflux when glucose is present. Moreover, incubation of lenses for 20 hrs. in the presence of cyanide fails to alter the internal concentration of calcium. The inhibition of glucose metabolism with iodoacetate (IAA) results in the accumulation of calcium to a level of 0.71mM and the formation of superficial subcapsular opacities. Evidence that fibers are also responsible for calcium extrusion consists of two findings: 1) removal of the epithelium from a lens results in calcium accumulation but the addition of IAA to such a lens results in a further gain in calcium; 2) the accumulation of 45Ca across the posterior surface of a lens partially immersed in medium is accelerated following inhibition of glycolysis.

Animals↗
PubMed1980

Calcium transport in the lens.

Evidence based on the following three observations suggests the existence of a calcium transport system in the mammalian lens: calcium levels in the lens are lower than that measured in the aqueous humor; calcium efflux is temperature-dependent and is reduced by inhibitors of Ca++ transport; and there exists a calcium-acivated, magnesium-dependent ATPase. In rat, bovine, dog, and rabbit lenses, the concentration of total calcium was found to be approximately 0.2 mM, at least an order of magnitude lower than that found in the aqueous humor. To determine the nature of the mechanism responsible for maintaining these low levels, calcium fluxes were measured. During the initial rapid phase of 45Ca efflux, the rate at 4 degrees C was reduced by 85% compared with that found at 37 degrees C. Efflux was not altered in the absence of external Na+. Calcium efflux was reduced, however, by lanthanum and propranolol, inhibitors of Ca/Mg ATPase. The presence of Ca/Mg ATPase was also demonstrated in the rat, bovine, and rabbit lens and was likewise inhibited by both lanthum and propranolol.

Animals↗
PubMed1978

Studies on the crystalline lens. XXVI. Kinetic study showing saturation of the sodium pump.

Active transport of sodium out of rabbit lenses was shown to be carrier mediated by observing the dependence of efflux of 22Na on intracellular concentration of nonlabeled sodium which previously was elevated by incubating lenses at 0 degree C. Velocity of sodium efflux increased asymptotically with increasing concentrations of intracellular sodium, demonstrating saturation of the carrier. The maximum velocity of the sodium pump based on Michaelis-Menten kinetics was found to be 4.6 mumol/hr/lens, and the half-saturation of the carrier, which appeared to involve a single site, occurred at 36 mM.

Animals↗