Disease relevance of canavanine

• Cumulative toxicity was reduced greatly when canavanine was administered at a dose level of 2.0 g/kg for 5 days (weight loss of 13%) [1].
• Analysis of the relationship of caloric deprivation to tumor growth reduction established that canavanine-mediated curtailment of tumor growth was not caused by reduced food intake and its associated loss in body weight [1].
• In Escherichia coli, Lon protease is responsible for the rate-limiting step in degradation of highly unstable proteins such as SulA, RcsA, and lambdaN protein, as well as for about 50% of the rapid degradation of abnormal proteins such as canavanine-containing proteins [2].
• The function of ScRheb is dependent on having an intact effector domain since mutations in the effector domain of ScRheb are incapable of complementing canavanine hypersensitivity of scrheb disruptant cells [3].
• Adeno-associated virus replication. The effect of L-canavanine or a helper virus mutation on accumulation of viral capsids and progeny single-stranded DNA [4].

Psychiatry related information on canavanine

• L-Canavanine (200 mg/kg, i.p.) did not affect the pain threshold, morphine-induced analgesia and the induction and expression phases of morphine tolerance and dependence [5].
• CONCLUSION: Chronic L-NAME administration, but not L-canavanine, had detrimental effects on the severity of hepatic damage and motor activities in TAA-treated rats [6].

High impact information on canavanine

• Pro-opiomelanocortin that accumulated in the presence of canavanine was also sulfated [7].
• The arginyl-tRNA synthetase of the bruchid beetle larvae discriminates between L-arginine and L-canavanine, and canavanyl proteins are not synthesized [8].
• Such hypothesis is confirmed by our in vivo experiments, showing that the administration of the NOS inhibitor L-canavanine to endothelioma-bearing mice significantly reduced both the volume and the relapse time of the tumor [9].
• Strains selectively mutagenized in this site display a mutator phenotype detected as a drastically increased spontaneous forward mutation rate to canavanine resistance or as an elevated reversion rate to lysine prototrophy [10].
• Both the size and the structure of the PP precursor was supported by the results of peptide analysis of biosynthetically labeled pro-PP isolated from canine PP cells in which processing was prevented by the arginine analogue canavanine [11].

Chemical compound and disease context of canavanine

• L-Canavanine is a potentially deleterious arginine antimetabolite whose toxicity is expressed in canavanine-sensitive organisms ranging from viruses to humans [12].
• Furthermore, the conserved arginine in the G1 box plays a role in the activity of ScRheb, as a mutation of this arginine to glycine significantly reduced the ability of ScRheb to complement canavanine hypersensitivity of ScRheb-deficient yeast [3].
• Treatments known to stimulate the synthesis of heat shock proteins (carotid occlusion, hyperthermia, Cd2+, canavanine, and ethanol) induced ODC activity in the liver, whereas only hyperthermia and ethanol caused significant increases in spleen ODC activity [13].
• Effects of dexamethasone and L-canavanine on the intracellular calcium-contraction relation of the rat tail artery during septic shock [14].
• In contrast to L-canavanine, nitro-L-arginine methyl ester increased blood pressure at the expense of a severe fall in cardiac index, while largely enhancing lactic acidosis [15].

Biological context of canavanine

• Transfection of the CAT minigenes into RPMI 2650 cells and canavanine-resistant variants of this cell line yielded no difference in transient CAT expression [16].
• This finding suggested that frequent injections of high doses of canavanine would be required for an effect on tumor cell proliferation [17].
• The interaction between L-canavanine treatment and gamma-ray damage with respect to cell survival was examined under several conditions and times based on the above findings [18].
• We analyzed the effects of procainamide (PROC), hydralazine (HYD), N-acetylprocainamide (NAPA), and L-canavanine (CAN) on circular supercoiled plasmids as models for chromosomal loop domains [19].
• At low concentrations of Ritonavir (5 microM) cells were more sensitive to canavanine but proliferated normally whereas at higher concentrations (50 microM) protein degradation was affected, and the cell cycle was arrested in the G(1)/S phase [20].

Anatomical context of canavanine

• Canavanine inhibits vimentin assembly but not its synthesis in chicken embryo erythroid cells [21].
• Continued exposure of the fat body to canavanine decreases in vitro protein secretion but the proportion of canavanyl vitellogenin to native vitellogenin increases [22].
• Double-label protein-turnover experiments with larvae injected with [14C]canavanine- and [3H]arginine-containing hemolymph proteins showed that canavanine-containing proteins were degraded preferentially [23].
• Furthermore, cloned canavanine-resistant variant cells having integrated copies of the CAT minigenes expressed CAT at similar levels as compared to the parental cell lines [16].
• Using the human colonic tumor cell line, HT-29, time-dose studies were performed with log-phase cultures in order to determine conditions which maximize the incorporation of L-canavanine into cellular proteins while leaving a large fraction of the cells viable for subsequent gamma-ray survival measurements [18].

Associations of canavanine with other chemical compounds

• Canaline reductase performs at least three important functions for canavanine-synthesizing legumes [24].
• Canavanine-storing legumes contain arginase, which hydrolyzes L-canavanine to form the toxic metabolite L-canaline [24].
• Furthermore, sequence analysis of UVA-induced canavanine-resistant mutations reveals a bias in favor of GC-->TA events when compared with spontaneous or H(2)O(2)-, UVC-, and gamma-ray- induced canavanine-resistant mutations in the WT strain [25].
• Cells expressing mutant versions of ubiquitin were found to be sensitive to cadmium, an agent that causes oxidative damage to cellular components, and to canavanine, an amino acid analog that generates misfolded proteins [26].
• 2. The enzyme also catalyzes the hydrolysis of L-canavanine, Nalpha-methyl-L-argine, D-arginine, L-homoarginine, L-argininic acid, and guanidine, in order of decreasing second order rate constants (kcat/Km); the second order rate constants for these substrates are 10(-3) to 10(-10) smaller than the rate constant for L-arginine [27].

Gene context of canavanine

• APOBEC3G expression caused a 20-fold increase in frequency of mutation to canavanine-resistance, which was further elevated in a uracil DNA glycosylase-deficient background [28].
• This gene, which we have designated STI1, for stress inducible, was also induced by the amino acid analog canavanine and showed a slight increase in expression as cells moved into stationary phase [29].
• Disruption of the MLH1 gene results in elevated spontaneous mutation rates during vegetative growth as measured by forward mutation to canavanine resistance and reversion of the hom3-10 allele [30].
• Genetic analysis of Saccharomyces cerevisiae also has identified a role for Rad27p in mutation avoidance. rad27Delta mutants display both a repeat tract instability phenotype and a high rate of forward mutations to canavanine resistance that result primarily from duplications of DNA sequences that are flanked by direct repeats [31].
• Although rad23Delta rpn10Delta displays similar sensitivity to DNA damage as a rad23Delta single mutant, deletion of RAD23 in rpn10Delta significantly increased sensitivity to canavanine, a phenotype associated with an rpn10Delta single mutant [32].

Analytical, diagnostic and therapeutic context of canavanine

• The reduction in tumor volume, expressed as the percentage of regression, was 22% in animals receiving canavanine, 3.0 g/kg daily for 5 days and 60% in the 3.0-g/kg-daily-for-9-days treatment group [1].
• Both the intracellular and secreted albumin produced by canavanine-treated cells were analyzed by DEAE-cellulose chromatography and were found to be more acidic than normal proalbumin and albumin [33].
• In the present study, we evaluated the effects of L-canavanine, a selective iNOS inhibitor, in an animal model of septic shock, with a particular focus on tissue oxidative metabolism and organ functions [34].
• The relation was restored by dexamethasone (which also restored in vivo blood pressure and flow), but not by L-canavanine (which restored perfusion pressure by further mobilization of intracellular Ca2+) [14].
• Synchronized cell cultures were infected with 32P-labelled or unlabelled BPV in the presence or absence of aphidicolin and L-canavanine [35].

References