Dictyostelium discoideum Fatty-acyl Amidase II Has Deacylase Activity on Rhizobium Nodulation Factors

Sutherland, Peggy J.; Tobin, Andrea; Rutherford, Charles L.; Price, N. P. J.

doi:10.1074/jbc.273.8.4459

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…It is possible that the function of O-acetyl or Nmethyl substituents on the nonreducing terminus is thus to render LCOs more resistant to degradation. This proposal is supported by the recent finding that LCOs produced by Rhizobium fredii (a strain that produces non-N-methylated LCOs) are de-N-acylated by fatty acyl amidase II secreted by Dictyostelium discoideum but, interestingly, N-methylated LCOs from a transgenic R. fredii strain carrying nodS are protected against degradation by this enzyme (31).…”

Section: Discussionsupporting

confidence: 66%

Rhizobial NodL O -Acetyl Transferase and NodS N -Methyl Transferase Functionally Interfere in Production of Modified Nod Factors

et al. 2001

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The products of the rhizobial nodulation genes are involved in the biosynthesis of lipochitin oligosaccharides (LCOs), which are host-specific signal molecules required for nodule formation. The presence of an O-acetyl group on C-6 of the nonreducing N-acetylglucosamine residue of LCOs is due to the enzymatic activity of NodL. Here we show that transfer of the nodL gene into four rhizobial species that all normally produce LCOs that are not modified on C-6 of the nonreducing terminal residue results in production of LCOs, the majority of which have an acetyl residue substituted on C-6. Surprisingly, in transconjugant strains of Mesorhizobium loti, Rhizobium etli, and Rhizobium tropici carrying nodL, such acetylation of LCOs prevents the endogenous nodS-dependent transfer of the N-methyl group that is found as a substituent of the acylated nitrogen atom. To study this interference between nodL and nodS, we have cloned the nodS gene of M. loti and used its product in in vitro experiments in combination with purified NodL protein. It has previously been shown that a chitooligosaccharide N deacetylated on the nonreducing terminus (the so-called NodBC metabolite) is the preferred substrate for NodS as well as for NodL. Here we show that the NodBC metabolite, acetylated by NodL, is not used by the NodS protein as a substrate while the NodL protein can acetylate the NodBC metabolite that has been methylated by NodS.Rhizobial bacteria have the unique ability to induce formation of nitrogen-fixing nodules on the roots or stems of leguminous plants. The development of legume nodules is largely controlled by reciprocal signal exchange between the symbiotic partners. Legume roots secrete specific flavonoids or isoflavonoids that induce the transcription of many bacterial genes (nod, nol, and noe genes). Most of these genes are involved in the synthesis and secretion of signal molecules that are essential to trigger nodule formation and that are known as Nod factors. Nod factors from many rhizobial species have been characterized, and their structures have been elucidated. Because their basic structure consists of a chitin oligosaccharide backbone N acylated on the nonreducing terminal residue, they are referred to as lipochitin oligosaccharides (LCOs). The nature of the fatty acid and the combination of diverse chemical substitutions provide host specificity to the LCOs produced by a given rhizobial strain (for reviews, see references 1, 7, 9, and 25).

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Section: Discussionsupporting

confidence: 66%

Rhizobial NodL O -Acetyl Transferase and NodS N -Methyl Transferase Functionally Interfere in Production of Modified Nod Factors

et al. 2001

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“…Furthermore it is noteworthy that upon tissue distribution, Glupamid is readily N‐deacylated by specific amidases, i.e. intracellular enzymes releasing GL in the intracellular compartment [7]. GL is known to normalize biosynthesis of the substrates required to restore the functional ability of a joint.…”

Section: Discussionmentioning

confidence: 99%

G01 Glupamid: a novel nutraceutical approach to canine and feline osteoarthritis

Miolo¹,

Badino

Barbero

2006

Vet Pharm & Therapeutics

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“…Chemically speaking, PGA is the amide of palmitic acid and glucosamine and a highly lipophilic compound with a predicted logP value of 5.6 [20]. Similarly to fatty acid amides, it is hydrolysed by fatty acid amide hydrolases [21, 22], resulting in the intracellular release of glucosamine. PGA might thus exert a dual effect, i.e., the ALIA effect down-modulating cell hyperactivity [18] and the putative effect of glucosamine on the anabolic/catabolic balance of cartilage [23, 24].…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain

et al. 2019

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BackgroundOsteoarthritis is increasingly recognized as the result of a complex interplay between inflammation, chrondrodegeneration, and pain. Joint mast cells are considered to play a key role in orchestrating this detrimental triad. ALIAmides down-modulate mast cells and more generally hyperactive cells. Here we investigated the safety and effectiveness of the ALIAmide N-palmitoyl-d-glucosamine (PGA) in inflammation and osteoarthritis pain.MethodsAcute toxicity of micronized PGA (m-PGA) was assessed in rats following OECD Guideline No.425. PGA and m-PGA (30 mg/kg and 100 mg/kg) were orally administered to carrageenan (CAR)-injected rats. Dexamethasone 0.1 mg/kg was used as reference. Paw edema and thermal hyperalgesia were measured up to 6 h post-injection, when also myeloperoxidase activity and histological inflammation score were assessed. Rats subjected to intra-articular injection of sodium monoiodoacetate (MIA) were treated three times per week for 21 days with PGA or m-PGA (30 mg/kg). Mechanical allodynia and motor function were evaluated at different post-injection time points. Joint histological and radiographic damage was scored, articular mast cells were counted, and macrophages were immunohistochemically investigated. Levels of TNF-α, IL-1β, NGF, and MMP-1, MMP-3, and MMP-9 were measured in serum using commercial colorimetric ELISA kits. One- or two-way ANOVA followed by a Bonferroni post hoc test for multiple comparisons was used.ResultsAcute oral toxicity of m-PGA resulted in LD50 values in excess of 2000 mg/kg. A single oral administration of PGA and m-PGA significantly reduced CAR-induced inflammatory signs (edema, inflammatory infiltrate, and hyperalgesia), and m-PGA also reduced the histological score. Micronized PGA resulted in a superior activity to PGA on MIA-induced mechanical allodynia, locomotor disability, and histologic and radiographic damage. The MIA-induced increase in mast cell count and serum level of the investigated markers was also counteracted by PGA and to a significantly greater extent by m-PGA.ConclusionsThe results of the present study showed that PGA is endorsed with anti-inflammatory, pain-relieving, and joint-protective effects. Moreover, it proved that particle size reduction greatly enhances the activity of PGA, particularly on joint pain and disability. Given these results, m-PGA could be considered a valuable option in the management of osteoarthritis.

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Dictyostelium discoideum Fatty-acyl Amidase II Has Deacylase Activity on Rhizobium Nodulation Factors

Cited by 6 publications

References 25 publications

Rhizobial NodL O -Acetyl Transferase and NodS N -Methyl Transferase Functionally Interfere in Production of Modified Nod Factors

Rhizobial NodL O -Acetyl Transferase and NodS N -Methyl Transferase Functionally Interfere in Production of Modified Nod Factors

G01 Glupamid: a novel nutraceutical approach to canine and feline osteoarthritis

Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain

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Dictyostelium discoideum Fatty-acyl Amidase II Has Deacylase Activity on Rhizobium Nodulation Factors

Cited by 6 publications

References 25 publications

Rhizobial NodL O -Acetyl Transferase and NodS N -Methyl Transferase Functionally Interfere in Production of Modified Nod Factors

Rhizobial NodL O -Acetyl Transferase and NodS N -Methyl Transferase Functionally Interfere in Production of Modified Nod Factors

G01 Glupamid: a novel nutraceutical approach to canine and feline osteoarthritis

Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain

Contact Info

Product

Resources

About

G01 Glupamid: a novel nutraceutical approach to canine and feline osteoarthritis