Specific inhibition of the enzymic decarboxylation of <i>S</i>-adenosylmethionine by methylglyoxal bis(guanylhydrazone) and related substances

Corti, Angelo; Dave, C.; Williams-Ashman, H.G.; Mihich, Enrico; Schenone, Amelia

doi:10.1042/bj1390351

Cited by 120 publications

(47 citation statements)

References 21 publications

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“…To determine whether L. pneumophila requires the activity of host SAMDC during intracellular growth in mammalian cells, we infected cells treated with two inhibitors of polyamine biosynthesis. MGBG acts as a specific, competitive, and irreversible inhibitor of SAMDC (19,88,90), and DFMO is an irreversible inhibitor of ornithine decarboxylase (56,70), an enzyme required for the synthesis of putrescine, a precursor of spermidine. We initially found that treatment of mouse L929 cells with MGBG significantly inhibited L. pneumophila intracellular replication at 24 and 48 h postinfection, whereas DFMO inhibition was significant only at 48 h postinfection (Fig.…”

Section: Htpb Reaches the Cytosol Of L Pneumophila-infected Cellsmentioning

confidence: 99%

Legionella pneumophilaRequires Polyamines for Optimal Intracellular Growth

et al. 2011

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The Gram-negative intracellular pathogen Legionella pneumophila replicates in a membrane-bound compartment known as the Legionella-containing vacuole (LCV), into which it abundantly releases its chaperonin, HtpB. To determine whether HtpB remains within the LCV or reaches the host cell cytoplasm, we infected U937 human macrophages and CHO cells with L. pneumophila expressing a translocation reporter consisting of the Bordetella pertussis adenylate cyclase fused to HtpB. These infections led to increased cyclic AMP levels, suggesting that HtpB reaches the host cell cytoplasm. To identify potential functions of cytoplasmic HtpB, we expressed it in the yeast Saccharomyces cerevisiae, where HtpB induced pseudohyphal growth. A yeast-twohybrid screen showed that HtpB interacted with S-adenosylmethionine decarboxylase (SAMDC), an essential yeast enzyme (encoded by SPE2) that is required for polyamine biosynthesis. Increasing the copy number of SPE2 induced pseudohyphal growth in S. cerevisiae; thus, we speculated that (i) HtpB induces pseudohyphal growth by activating polyamine synthesis and (ii) L. pneumophila may require exogenous polyamines for growth. A pharmacological inhibitor of SAMDC significantly reduced L. pneumophila replication in L929 mouse cells and U937 macrophages, whereas exogenously added polyamines moderately favored intracellular growth, confirming that polyamines and host SAMDC activity promote L. pneumophila proliferation. Bioinformatic analysis revealed that most known enzymes required for polyamine biosynthesis in bacteria (including SAMDC) are absent in L. pneumophila, further suggesting a need for exogenous polyamines. We hypothesize that HtpB may function to ensure a supply of polyamines in host cells, which are required for the optimal intracellular growth of L. pneumophila.Chaperonins constitute a family of highly conserved proteins found in all prokaryotic and eukaryotic organisms (34). Their primary role is to facilitate the folding of nascent and stressdenatured proteins into their functional native states in an ATP-dependent manner (54). Group I chaperonins, referred to as Hsp60, Cpn60, or GroEL, are prokaryotic proteins found in bacteria and in eukaryotic organelles such as mitochondria and chloroplasts (34). Group II chaperonins, also known as CCT or TCP-1, are found in the eukaryotic cytosol and in the archaea (34). Structural and functional studies of Escherichia coli GroEL have established the role of group I chaperonins as intracellular mediators of protein folding (7, 94). GroEL is an essential protein in E. coli (23) whose intracellular level increases substantially in response to defined stressful stimuli (55, 85). The protein-folding paradigm of group I chaperonins has changed with accumulating reports of surface-and membrane-associated chaperonins that perform other diverse functions. For instance, the extracytoplasmically localized chaperonins of Haemophilus ducreyi (25), Helicobacter pylori (9, 92), Borrelia burgdorferi (77), and Clostridium difficile (37) have been implica...

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Section: Htpb Reaches the Cytosol Of L Pneumophila-infected Cellsmentioning

confidence: 99%

Legionella pneumophilaRequires Polyamines for Optimal Intracellular Growth

et al. 2011

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“…ACC as an immediate precursor of ethylene 13 ) and NAA induced as the same levels of sterility as that in the control. Spermine and MGBG, 14,15) which are related to the regulation of ethylene production, induced sterility similar to that in the control. Azetidine-2-carboxylic acid, which is an analogue of azetidine-3-carboxylic acid that induced male sterility in wheat, 3) produced no effect on sterility in rice.…”

Section: Effects Of Twelve Chemicals On Sterility In Ricementioning

confidence: 87%

Sterility in Rice Induced by Chemical Treatment

Shimada

Nagai

Kimura

1992

Bioscience, Biotechnology, and Biochemistry

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“…La S-adenosylmethionine decarboxylase (SAMDC), qui transforme Ia SAM en SAM decarboxylee {donneuse de groupements aminopropyles), est inhibee par le methylglyoxal-bis-{guanylhy-drazone) (MGBG), qui est un inhibiteur competitif in vitro et in vivo (WilliamsAshman et Schenone, 1972 ;Corti et al, 1974 (Sunkara et al, 1977;Heby 1981), puis dans les cellules vegetales (Flores et Galston, 1982 ;Martin-Tanguy, 1985;Bagni 1988 (Taboret Tabor, 1976;Pegg et Me Cann, 1982). L'activite de l'ODC est corrclce positivement avec Ia division cellulaire dans les cultures de cellulcs de tabac alors que celle de I'ADC se trouve tres reduite (Heimer et al, 1979).…”

Section: Metabolisme Des Polyaminesunclassified

Métabolisme et rôle des polyamines dans le développement de la plante

Daoudi¹,

Biondi

1995

Acta Botanica Gallica

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Summary.-Aliphatic polyamines, putrescine, spermidine and spermine are ubiquHous in all living organisms. They occur in the free form as cations, but are often conjugated to small molecule like phenolics acids and also to various macromolecules. Polyamines and their biosynthetic enzymes may play an imponant role in many aspects of plants development including growth, differentiation, senescence and response to dillerents types of stress. Recent worl< suggest, but has not proven, a regulatory role of polyamines in these processes. Putrescine accumulation in response to stress, suggests a protective role. By contrast, increased spermidine and spermine synthesis appears essential for DNA replication and cell division.

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Specific inhibition of the enzymic decarboxylation of S-adenosylmethionine by methylglyoxal bis(guanylhydrazone) and related substances

Cited by 120 publications

References 21 publications

Legionella pneumophilaRequires Polyamines for Optimal Intracellular Growth

Legionella pneumophilaRequires Polyamines for Optimal Intracellular Growth

Sterility in Rice Induced by Chemical Treatment

Métabolisme et rôle des polyamines dans le développement de la plante

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