Specific changes in lactate levels, lactate dehydrogenase patterns and cytochrome b559 in Dictyostelium discoideum caused by queuine

Schachner, Elfriede; Aschhoff, H. J.; Kersten, H.

doi:10.1111/j.1432-1033.1984.tb08031.x

Cited by 24 publications

(11 citation statements)

References 37 publications

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“…In lower and higher eukaryotes q andor Q-containing tRNAs have been suggested to be involved in the adaptation of cellular metabolism to aerobiosis and hypoxia [9,10,15,17,42,431. However, it was not clear whether the observed metabolic changes were the consequence of alterations of Q modification of the respective tRNAs or of free q.…”

Section: Discussionmentioning

confidence: 99%

The nutrient factor queuine protects HeLa cells from hypoxic stress and improves metabolic adaptation to oxygen availability

Reisser

Langgut

Kersten

1994

European Journal of Biochemistry

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Queuine (q), a cyclopentendiol derivative of 7-aminomethyl-7-deazaguanine, is a nutrient factor for lower and higher eukaryotes, except yeast; it is synthesized in eubacteria partly at the level of tRNA. In eukaryotes q is preferentially inserted into the wobble position of specific tRNAs in differentiated and adult tissues, but occurs mainly free in embryonic and fast proliferating cells. HeLa cells grow to a higher cell densitiy under aerobic than under hypoxic conditions only when supplemented with q. Here we show that in hypoxically grown HeLa cells, sufficiently supplied with q, free q accumulated when serum factors become limiting while the respective tRNAs remained completely q deficient. In these cells the levels of lactate dehydrogenase A (LDH A) mRNA and of LDH A protein were at least twofold higher than in aerobically grown cells, independent of the absence or presence of q. In response to q the LDH A, isoenzyme was further activated by a post-translational mechanism. In q-deficient HeLa cells the activity of the major anoxic stress protein, LDHk, increased as a result of hypoxia; this increase was suppressed by q. In aerobically grown, q-deficient cells significant activities of LDH A, and LDH, were present ; both activities were markedly lowered by q, while the mitochondrial electron flow was improved. The results show that free q is essential for relieving hypoxic stress in HeLa cells that results from oxygen limitation. The modified base queuine [q; 7-5-( [(lS,4S,5R)-4,5-di-anine], is synthesized in eubacteria only. During the biosynthesis GTP is converted to the precursor 7-aminomethyl-7-deazaguanine by so far unknown steps. The tRNA guanine transglycosylase (Tgt) exchanges this precursor specifically for the guanine residue in the anticodons GUN of tRNAs specifying the amino acids Asn, Asp, His and Tyr [l]. The cyclopentendiol moiety is derived from the ribose residue of S-adenosylmethionine and is attached to the modified tRNA precursor by a novel AdoMet-dependent reaction that is catalyzed by the tRNA ribosyltransferase-isomerase (QueA) [2]. During the QueA reaction, epoxy-queuosine is formed that is finally reduced to queuosine (Q) by a vitamin-B ,,-dependent, unidentified enzyme [3]. The genes, tgt and queA, are localized on the Escherichia coli genome in one operon [4].Mammals obtain q from nutrients or the intestinal flora [5-91. Specific eukaryotic Tgt enzymes insert the q-factor in a practically irreversible reaction into the wobble position of cytosolic and of mitochondrial tRNA,,, species [5-71.

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Section: Discussionmentioning

confidence: 99%

The nutrient factor queuine protects HeLa cells from hypoxic stress and improves metabolic adaptation to oxygen availability

Reisser

Langgut

Kersten

1994

European Journal of Biochemistry

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“…A major structural change in the anticodon of tRNAs (such as queuine versus guanine) has the potential to alter mRNA codon recognition and, as a result, gene expression. In fact, changes in queuine modification of tRNA have been implicated in playing some role in cell differentiation and neoplasia (8,9,11,29), but much of the existing evidence is only circumstantial.The present study was undertaken to determine whether alterations in queuine modification of tRNA are involved in the differentiation of HGPRT-deficient HL-60 cells induced by 6-thioguanine and related compounds known to be substrates for tRNA-guanine ribosyltransferase. …”

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Guanine analog-induced differentiation of human promyelocytic leukemia cells and changes in queuine modification of tRNA.

1987

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Treatment of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient human promyelocytic leukemia (HL-60) cells with 6-thioguanine results in growth inhibition and cell differentiation. 6-Thioguanine is a substrate for the tRNA modification enzyme tRNA-guanine ribosyltransferase, which normally catalyzes the exchange of queuine for guanine in position 1 of the anticodon of tRNAs for asparagine, aspartic acid, histidine, and tyrosine. During the early stages of HGPRT-deficient HL-60 cell differentiation induced by 6-thioguanine, there was a transient decrease in the queuine content of tRNA, and changes in the isoacceptor profiles of tRNAHis indicate that 6-thioguanine was incorporated into the tRNA in place of queuine. Reversing this structural change in the tRNA anticodon by addition of excess exogenous queuine reversed the 6-thioguanine-induced growth inhibition and differentiation. Similar results were obtained when 8-azaguanine (another inhibitor of queuine modification of tRNA that can be incorporated into the anticodon) replaced 6-thioguanine as the inducing agent. The data suggest a primary role for the changes in queuine modification of tRNA in mediating the differentiation of HGPRT-deficient HL-60 cells induced by guanine analogs.A wide variety of agents are known to induce the differentiation of leukemia cells in vitro (5,7,14,15,22), but the molecular mechanisms responsible for such chemically induced maturation are, for the most part, obscure. With murine erythroleukemia cells and human promyelocytic leukemia (HL-60) cells, the purine antimetabolite 6-thioguanine is a highly effective inducing agent only if the cells lack the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (13,14,30). Since HGPRT deficiency should impair the formation of 6-thioguanine nucleotides, Gusella and Housman (14) proposed that the generation of these cytotoxic nucleotides and their subsequent incorporation into DNA are probably not involved in the differentiation sequence. Recent work by Ishiguro et al. (17) verified that 6-thioguanine itself was capable of inducing the differentiation of HGPRT-deficient HL-60 cells, while wild-type HL-60 cells metabolized the guanine analog to the expected cytotoxic nucleotides. Although these studies demonstrated that 6-thioguanine was the metabolic form responsible for the induction of differentiation of HGPRT-deficient HL-60 cells, the molecular basis for this induction was not established.Many purine analogs, including 6-thioguanine, have been reported to be substrates for the tRNA modification enzyme tRNA-guanine ribosyltransferase (EC 2.4.2.29) (12,33). This enzyme catalyzes the exchange of the highly modified purine analog queuine [7-([3S,4R,5S]-4,5-dihydroxy-2-cyclopent-1-en-3-ylaminomethyl)-7-deazaguanine] for the major base guanine via direct base replacement, whereby the phosphodiester backbone of the tRNA is not broken (1,11,21 obtain this factor from the sera used to supplement the cell culture medium (18,20). The queuine exchange reaction o...

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“…LDH k/6 activity is suppressed by the modified base queuine [126]. Specific changes in LDH level and isoenzyme pattern by queuine are observed in D. discoidium [127] and in cancerous mice [128,129] to down-regulate anaerobic metabolism. Queuine protects HeLa cells from hypoxic stress and improves metabolic adaptation [18,130].…”

Section: Regulation Of Glycolytic Metabolism By Queuinementioning

confidence: 93%

Queuosine modification of tRNA: its divergent role in cellular machinery

Vinayak

Pathak

2009

Bioscience Reports

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tRNAs possess a high content of modified nucleosides, which display an incredible structural variety. These modified nucleosides are conserved in their sequence and have important roles in tRNA functions. Most often, hypermodified nucleosides are found in the wobble position of tRNAs, which play a direct role in maintaining translational efficiency and fidelity, codon recognition, etc. One of such hypermodified base is queuine, which is a base analogue of guanine, found in the first anticodon position of specific tRNAs (tyrosine, histidine, aspartate and asparagine tRNAs). These tRNAs of the 'Q-family' originally contain guanine in the first position of anticodon, which is post-transcriptionally modified with queuine by an irreversible insertion during maturation. Queuine is ubiquitously present throughout the living system from prokaryotes to eukaryotes, including plants. Prokaryotes can synthesize queuine de novo by a complex biosynthetic pathway, whereas eukaryotes are unable to synthesize either the precursor or queuine. They utilize salvage system and acquire queuine as a nutrient factor from their diet or from intestinal microflora. The tRNAs of the Q-family are completely modified in terminally differentiated somatic cells. However, hypomodification of Q-tRNA (queuosine-modified tRNA) is closely associated with cell proliferation and malignancy. The precise mechanisms of queuine- and Q-tRNA-mediated action are still a mystery. Direct or indirect evidence suggests that queuine or Q-tRNA participates in many cellular functions, such as inhibition of cell proliferation, control of aerobic and anaerobic metabolism, bacterial virulence, etc. The role of Q-tRNA modification in cellular machinery and the signalling pathways involved therein is the focus of this review.

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Specific changes in lactate levels, lactate dehydrogenase patterns and cytochrome b₅₅₉ in Dictyostelium discoideum caused by queuine

Cited by 24 publications

References 37 publications

The nutrient factor queuine protects HeLa cells from hypoxic stress and improves metabolic adaptation to oxygen availability

The nutrient factor queuine protects HeLa cells from hypoxic stress and improves metabolic adaptation to oxygen availability

Guanine analog-induced differentiation of human promyelocytic leukemia cells and changes in queuine modification of tRNA.

Queuosine modification of tRNA: its divergent role in cellular machinery

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