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Structural transitions of calf thymus DNA in concentrated LiCl solutions.

The solubility, sedimentation, circular dichroism, and absorption spectral characteristics of calf thymus DNA have been examined in concentrated solutions of LiCl (6-13 m) at 25 to 27 degree C. At all concentrations of LiCl, the DNA is base stacked and exhibits normal hypochromicty, At the upper end of this range of LiCl concentrations, DNA aggregates and ultimately precipitates completely from solution between 13 and 14 m LiCl. This aggregation process is dependent on concentration, base composition, and molecular weight of DNA. The sedimentation velocity data taken together with the absorbance spectral data suggest that the aggregation process leading to the formaiton of large structures beings at approximately equal to 9 m. Prior to the onset of aggregation, the circular dichroism (CD) spectra can be adequately fitted by a linear combination of contributions of the B, C, and A forms of DNA (Hanlon, S., Brudno, S., Wu, T. T., and Wolf, B. (1975), Biochemistry 14, 1648). Above 9 m LiCl, both factor analysis and a primitive version of matrix rank order analysis indicate that at least one additional spectral component is required to account for the observed CD spectra above 260 nm. The general shape of this additional component or distortion resembles the psi form of DNA.

Animals

LiCl induces GSK-3β mediated autophagy, DNA damage, and cell cycle arrest in HPV driven cervical cancer cells.

High-risk HPV infections induce cervical cancer progression by disrupting cellular homeostasis and survival pathways, including autophagy. Targeting autophagy represents a promising therapeutic strategy. Lithium chloride (LiCl), extensively studied for its neuroprotective properties, can be investigated for its potential anticancer effects in HPV-driven cervical cancer cells. Treatment with 30 mM LiCl induced significant phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9, inducing functional inhibition and downstream signal alterations. This modulation of GSK-3β activity compromised genomic integrity, validated by increased double strand DNA breaks, increased oxidative and cellular stress, and reduced antioxidant enzyme activity. Consequently, LiCl treated cells exhibited significant G2/M phase arrest, indicating disruption in cell cycle progression. Interestingly, the observed cytotoxicity occurred independently of classical apoptotic pathways, suggesting the activation of alternative cell death mechanisms. Mechanistic studies revealed a robust autophagic flux, with GSK-3β mediated autophagy, validated through siRNA mediated knockdown experiments. These findings highlight a novel cytotoxic mechanism of LiCl and propose its potential repurposing from neurobiology to targeted cancer therapeutics.

Humans

Effects of acute swim stress on LiCl-induced conditioned taste aversions.

The present study examined the effects of a 5-min period of swim stress experienced between a flavor (saccharin) and illness (LiCl) on conditioned taste aversion learning. Experiment 1 obtained a stress-induced attenuation of learning. Experiment 2 replicated the findings of Experiment 1, and also obtained a similar attenuation when stress was administered 30 min prior to the saccharin presentation. Experiment 3 examined the effects of swim stress either 15 min or 90 min after the LiCl had been administered. It was found that swim stress 15 min after LiCl significantly attenuated CTA, but swim stress 90 min after LiCl did not. These results are discussed with regard to current views of the relationship between external events and conditioned taste aversions.

Animals

NaCl and LiCl efficacy in the induction of aversion for quinine and saccharin solutions immediately following injection.

Rats 24-hr water deprived were injected IP with a fixed amount (10 ml/kg) of solution of various concentrations of LiCl and NaCl in dosage ranges which in previous experiments either increased or had no effect on water intake. Intake of 0.01% QHCl decreased with increasing concentrations of both NaCl and LiCl. On a molar basis, LiCl was more effeictive. LiCl also produced an aversion to a palatable solution, 0.1% sodium saccharin; however, NaCl produced no aversion over the dosage range which can be tolerated by the animals.

Animals

LiCl-induced selective depression of saccharin drinking in the mouse.

Water-deprived mice were injected with various concentrations of LiCl or NaCl 15 min before they were allowed to drink either water or 0.1% saccharin. The NaCl injections produced a dose-dependent increase in intake of both fluids: however, the higher dosages of LiCl produced a selective depression of fluid intakes. Saccharin intakes were depressed for less than one hr but water intakes were not affected. LiCl injections also depressed general activity and produced an apparent shift of water from blood into cells. The LiCl-induced depression of saccharin was not significantly influenced by extensive previous experience with the drinking fluid.

Animals

Role of brain amines in the fetal hyperpyrexia caused by tranylcypromine in LiCl-pretreated rats.

Tranylcypromine (TCP), a monoamine oxidase inhibitor, caused a fatal hyperpyrexia in rats pretreated with LiCl once a day for 4 days. Pretreatment with LiCl alone did not alter the level of serotonin (5-HT), dopamine (DA) and norepinephrine (NE) in the brain. In fatal hyperpyrexia caused by LiCl plus TCP, the brain 5-HT and DA levels were increased, whereas the brain NE level was decreased. Reserpine and alpha-methyl-p-tyrosine completely prevented the hyperpyrexia, but FLA-63 did not show any effect. The hyperpyrexia was completely prevented by p-chlorophenylalanine (PCPA) given 72 hours before TCP but not by PCPA given 24 hours before TCP. Haloperidol and chlorpromazine, DA receptor blockers, inhibited the fatal hyperpyrexia, while cyproheptadine and methysergide, 5-HT receptor blockers, did not. These results suggest that DA plays an essential role in the hyperpyrexia induced by the combination of TCP and LiCl in rats, but the involvement of 5-HT is inconclusive.

Amines

Learned aversion and rearing movement in rats given LiCl, PbCl2 or NaCl.

The effects of an i.p. injection of 0.15 M LiCl resembled closely the effects of another toxic substance, 0.005 M PbCl2, on conditioned aversion to saccharin and rearing movements in male rats. The findings suggest that nonspecific aversive after-effects of a LiCl injection can account fully for prompt effects of LiCl on rearing behavior.

Animals

Metrazol impairs conditioned aversion produced by LiCl: a time dependent effect.

The effects of 40 mg/kg Metrazol on a conditioned saccharin aversion produced by LiCl were studied in two experiments. In Experiment 1, it was found that Metrazol administered 10 min before or after LiCl did not impair conditioned aversion to saccharin. In Experiment 2, Metrazol was given 2 min before, 9 or 3 min after the administration of LiCl. Under these conditions, impairment did occur. It was concluded that Metrazol may impair conditioned taste aversion in a time-dependent manner. The present findings are discussed in terms of their relationship to ECS as an interfering agent and retroactive and proactive effects on the CS and/or the UCS.

Animals

Structure of LiCl core particles of 50 S ribosomal subunits from Escherichia coli by electron microscopy.

The structure of 50 S E. coli ribosomal subunits was studied by electron microscopy as these particles were gradually depleted of proteins by incubation with 0.5 to 6.0 m LiCl. Changes observed in the structure of the depleted subunits were correlated with the location of the deleted ribosomal proteins on the control 50 S particle. These changes were particularly striking in the "crown" region, the site of a considerable number of the proteins necessary for the biological activity of the 50 S subunit. Protein L 16, the first to be removed by the LiCl treatment, was found to be essential for the structural integrity of the large subunit through interactions with ribosomal proteins residing in the left-hand side crest and the interface. Based on electron microscopic evidence, a scheme was proposed for the structural changes accompanying the stepwise unfolding of the 50 S E. coli subunit by LiCl.

Bacterial Proteins

Purification and properties of a protein factor stimulating peptidoglycan synthesis in toluene- and Licl-treated Bacillus megaterium cells.

A protein factor, called PG-I, can be solubilized from toluene-treated Bacillus megaterium cells by LiCl extraction. After LiCl extraction, peptidoglycan synthesis by the toluene-treated cells is decreased. Protein PG-I can be added back to the extracted cells to stimulate peptidoglycan synthesis. This factor has now been purified 124-fold. It has a molecular weight of 42,000 as estimated by Sephadex gel filtration in the presence of 0.4 M KCl and 52,000 as determined by sodium dodecyl sulfate disc gel electrophoresis. Periodate-Schiff staining of the polyacrylamide gel indicates that factor PG-I is a glycoprotein. The reconstitution of LiCl-extracted cells requires Mg2+ with an apparent Km of 1.9 X 10(-3) M. The Mg2+ ions can be replaced by Ca2+ and by Mn2+ ions to some extent; Zn2+ and Cu2+ ions had no effect. The available data suggest that factor PG-I is essential for peptidoglycan synthesis and requires at least one thiol group for stimulatory activity.

Bacillus megaterium

Defensive burying following injections of cholecystokinin, bombesin, and LiCl in rats.

Past research indicates that feeding is reduced for animals injected with cholecystokinin and bombesin. One explanation for this effect suggests that these peptides act as natural satiety signals; an opposing view asserts that bombesin and cholecystokinin reduce feeding through malaise. The present experiment tested the basic assumptions associated with these positions using the defensive burying procedure. Groups of rats were given sweetened condensed milk followed by IP injections of bombesin (6, 16, and 32 micrograms/kg), cholecystokinin (0.7, 1.4, and 2.9 micrograms/kg), LiCl (6.4 mg/ml), or saline. The results showed that animals injected with cholecystokinin, bombesin, and LiCl developed learned aversions to the milk and actively buried the milk spout with their bedding. The findings provide further support for the view that bombesin and cholecystokinin induce malaise rather than satiety.

Animals

Incubation of myosin with exogenous small components (g1, g2, or g3) in KSCN or LiCl and properties of g-exchanged myosins.

Myosin was incubated with a large excess of exogenous g1, g2 or g3 in 0.6 M KSCN (or in 4 M LiCl) for 1-2 h at 0-2 degrees C. KSCN (or LiCl) was then removed by dialysis. The composition of g-chains in the resulting myosin was analyzed by SDS-gel electrophoresis. When myosin was incubated with g1, the amount of g1 in myosin increased and the increment was nearly counterbalanced by a decrease in g3, whereas an opposite change was observed on incubation with g3. The amount of g2 was not changed by these treatments. The same ATPase activity as that of control myosin was observed in the presence of Ca2+ or EDTA with the myosins incubated with g1, g2, or g3, but the activity in the presence of Mg2+ was about one-half of the control. The Ca2+ sensitivity of actomyosin containing the treated myosins was slightly higher than that of actomyosin containing the control myosin. Spin-labeled g1 or spin-labeled g3 was incorporated into myosin, but the ESR spectra of two spin labels were not distinguishable. No information could be obtained from the ESR spectra by the addition of Ca2+, Mg2+, nucleotides or actin. Inhibition of ATPase activity was observed when SH groups g1 or g3 in myosin were chemically modified.

Actins

Isolation of viral double-stranded RNAs using a LiCl fractionation procedure.

A general procedure for the isolation of virus-specific double-stranded RNA (ds-RNA) is discribed. The procedure is based on the differential solubility of different types of nucleic acids in LiCl. Principal advantages over conventional methods are simplicity, avoidance of enzymatic treatment, and relatively good yields of undegraded ds-RNA while permitting separation of several main groups of cellular and viral nucleic acids from the same batch of tissue. The method has been successfully applied in tissues infected by several representative plant RNA viruses. The virus-specific ds-RNAs obtained have been identified by their resistance to ribonuclease and comparison of their electrophoretic mobilities with those of the corresponding single-stranded RNA (ss-RNA) in polyacrylamide gels. The molecular weights of the ds-RNAs of tobacco mosaic virus, turnip yellow mosaic virus, alfalfa mosaic virus, and peanut stunt virus fit the curved log molecular weight-migration relationship constructed from a set of known marker ds-RNAs.

Chlorides

Interaction of ethidium bromide with DNA: effect of LiCl and ethylene glycol.

The interaction of the intercalating dye ethidium bromide with several native and synthetic polydeoxyribonucleic acids has been studied by means of circular dichroic spectra. The CD of DNA-ethidium bromide complexes in the 290-360 nm region is characterized, especially at high salt and at high ethylene glycol content, by positive and negative bands near 308 nm and 295 nm, respectively. These dye associated CD bands are unaffected by the addition of LiCl or ethylene glycol, suggesting that the relative conformation of dye and neighboring base pairs does not change when the conformation of the rest of the DNA changes.

Animals

Reconstitution of cell wall synthesis in toluene- and LiCl-treated Bacillus megaterium cells by addition of a soluble protein extract.

Proteins required for the synthesis of peptidoglycan and incorporation of diaminopimelic acid into cell walls have been solubilized from Bacillus megaterium toluene-treated cells. Some of these proteins might have been removed from the cytoplasmic membrane through the cell wall by extraction with LiCl. The solubilized proteins have molecular weights in the range of 40,000 to 70,000 and can be added back to B. megaterium toluene-treated cells to reconstitute the synthetic reactions.

Bacillus megaterium