Disease relevance of RRS1

• RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells involves Bax translocation to mitochondria [1].
• RRR-alpha-tocopheryl succinate inhibits human prostate cancer cell invasiveness [2].
• RRR-alpha-tocopheryl acetate supplementation at pharmacologic doses decreases low-density-lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus [3].
• By using a low-dose solar-simulated radiation protocol, we investigated whether oral supplementation of the antioxidants RRR-alpha-tocopherol combined with L-ascorbic acid prevented radiation-induced suppression of the contact hypersensitivity response to nickel sulfate [4].
• Therefore, the objective of the present study was to assess the effect of RRR-alpha-tocopheryl acetate supplementation on LDL oxidizability and protein glycation in persons with diabetes without evidence of vascular disease [3].

Psychiatry related information on RRS1

• Pooled analysis of all studies showed that PTS developed in 24% (61/254) in the compression group and in 46% (110/239) in the control group (chi2=25.36, p=0.0001; OR: 0.37, 95%CI: 0.25, 0.54; RR: 0.52, 95%CI: 0.40, 0.67; and RRR: 0.48, 95%CI: 0.33, 0.60) with a 48% risk reduction from the use of compression [5].
• Oral supplementation with all-Rac- and RRR-alpha-tocopherol increases vitamin E levels in human sebum after a latency period of 14-21 days [6].

High impact information on RRS1

• We identified an ER retention signal (RRR) in the C1 cassette of NR1, which is similar to the RXR motif in ATP-sensitive K(+) channels (Zerangue et al., 1999) [7].
• Increasing evidence suggests that the different chemical (e.g., alpha- and gamma-tocopherol) and stereochemical (e.g., RRR- and all-racemic-alpha-tocopherol) forms of vitamin E have distinct biologic potencies, pharmacokinetics, and different abilities to prevent neoplastic transformation [8].
• Plasma and lipoprotein alpha-tocopherol concentrations of four patients with familial isolated vitamin E deficiency and six control subjects were observed for 4 d after an oral dose (approximately 15 mg) of RRR-alpha-tocopheryl acetate labeled with six deuterium atoms (d6-tocopherol) [9].
• Human plasma vitamin E kinetics demonstrate rapid recycling of plasma RRR-alpha-tocopherol [10].
• In order to elucidate the molecular mechanism of the signaling pathway, we isolated a cold-sensitive mutant with a mutation in a gene termed RRS1 (regulator of ribosome synthesis), which appeared to be defective in the signaling pathway [11].

Chemical compound and disease context of RRS1

• Long-term oral vitamin E supplementation in cystic fibrosis patients: RRR-alpha-tocopherol compared with all-rac-alpha-tocopheryl acetate preparations [12].
• The RRR-alpha-tocopherol (vitamin E) content in plasma from 46 patients with liver diseases and 23 healthy controls was determined by high performance liquid chromatography and electrochemical detection [13].
• The ability to discriminate between stereoisomers of alpha-tocopherol was studied in five patients with abetalipoproteinemia (ABL) because an impairment in secretion of apolipoprotein B-containing lipoproteins might impede the normally enhanced plasma transport of RRR-alpha-tocopherol [14].
• Stereoisomers of alpha-tocopheryl acetate. III. Simultaneous determination of resorption-gestation and myopathy in rats as a means of evaluating biopotency ratios of all-rac- and RRR-alpha-tocopheryl acetate [15].
• RRR-alpha-tocopherol ether linked acetic acid analog (alpha-TEA), is a potential chemotherapeutic agent for ovarian cancer [16].

Biological context of RRS1

• RRS1 is a novel, essential gene encoding a nuclear protein of 203 amino acid residues that is conserved in eukaryotes [11].
• The role of hydrogen peroxide and RRR-alpha-tocopherol in smooth muscle cell proliferation [17].
• The earliest event brought by RRR-alpha-tocopherol in the signal transduction cascade contolling receptor mediated cell growth is the inhibition of the transcription factor AP-1, activated by phorbol esters [17].
• The inhibition of RRR-alpha-tocopherol of protein kinase C is not the consequence of a direct interaction but is due to a diminution, produced by RRR-alpha-tocopherol of the kinase phosphorylation [17].
• A tocopherol binding protein appears to be at the basis of the RRR-alpha-tocopherol, that discriminates between RRR-alpha-tocopherol and RRR-beta-tocopherol and initiates a cascade of events at the level of cell signal transduction leading to cell proliferation inhibition [17].

Anatomical context of RRS1

• The concentration of RRR-alpha-tocopherol from each form was maximal at approximately 27 h in red blood cells and, as seen with the plasma data, there was a large interindividual variability [18].
• RRR-alpha-Tocopherol is the major peroxyl radical scavenger in biological lipid phases such as membranes or low-density lipoproteins [19].
• We studied the effects of RRR-alpha-tocopherol and RRR-beta-tocopherol in smooth muscle cells from rat (line A7r5) and human aortas [20].
• Previously we have shown that RRR-alpha-tocopherol (AT) enrichment of human monocyte-derived macrophages inhibited OxLDL or AcLDL induced CD36 expression [21].
• In plots of RRR for one drug combination vs. that for a second drug combination, cell lines that have the same pump amplified should cluster, whereas those with amplification of (functionally) different drug-efflux pumps should segregate [22].

Associations of RRS1 with chemical compounds

• Taken together, these data show alpha-TEA to be a potent and stable proapoptotic agent for human ovarian tumor cells and suggest that endogenous ovarian esterases can hydrolyze the succinate moiety of VES, yielding RRR-alpha-tocopherol, an ineffective apoptotic-inducing agent [23].
• Furthermore, when NR2Delta2 subunits were cotransfected with either the NR1-4a or NR1-1a(AAA) mutant, lacking the ER retention motif (RRR), functional NMDA receptors were detected in the transfected HEK293 cells [24].
• The relative order of thermodynamic stability for the four types of triplex studied here is found to be DDD >> RRR > RDR >> DRD [25].
• My valedictory on the differences in biological potency between RRR-alpha-tocopheryl and all-rac-alpha-tocopheryl acetate [26].
• Subjects were randomly assigned to one of two groups: (1) placebos (PL) or (2) antioxidants (AO: 1000 mg vitamin C and 300 mg RRR-alpha-tocopheryl acetate) [27].

Analytical, diagnostic and therapeutic context of RRS1

• Differences in stability of the ester-linked succinate moiety of VES versus the ether-linked acetic acid moiety of alpha-TEA were demonstrated by high-performance liquid chromatography analyses that showed alpha-TEA to remain intact, whereas VES was hydrolyzed to the free phenol, RRR-alpha-tocopherol [23].
• The ability of the vitamin E (RRR-alpha-tocopherol) derivatives alpha-tocopheryl succinate (alpha-TOS) and alpha-tocopheryloxyacetic acid (alpha-TEA) to suppress tumor growth in preclinical animal models has recently led to increased interest in their potential use for treating human cancer [28].
• Comparison of plasma alpha and gamma tocopherol levels following chronic oral administration of either all-rac-alpha-tocopheryl acetate or RRR-alpha-tocopheryl acetate in normal adult male subjects [29].
• In a randomized, crossover study subjects underwent two 4-week treatments (400 mg/day) with undeuterated RRR- and all rac-alpha-tocopheryl acetate around a 12-week washout [30].
• Effects of interaction of RRR-alpha-tocopheryl acetate and fish oil on low-density-lipoprotein oxidation in postmenopausal women with and without hormone-replacement therapy [31].

References