Inhibition of lymphocyte cyclic AMP phosphodiesterase and lymphocyte function by 5′-methylthioadenosine

Wolberg, Gerald; Zimmerman, Thomas P.; Schmitges, Claus J.; Duncan, Gail S.; Deeprose, Robert D.

doi:10.1016/0006-2952(82)90518-4

Cited by 13 publications

(3 citation statements)

References 18 publications

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“…Interestingly, of the 40 metabolites produced by K. slooffiae , 5′-methylthioadenosine (Fig. 7 D) contributed to the activation of cAMP-PKA signaling, as reported previously [ 59 , 60 , 96 ]. Our results demonstrated that 5′-methylthioadenosine decreased lysine succinylation levels in IPEC-J2 cells (Fig.…”

Section: Resultssupporting

confidence: 82%

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Core-predominant gut fungus Kazachstania slooffiae promotes intestinal epithelial glycolysis via lysine desuccinylation in pigs

Chen²,

Hou

et al. 2023

Microbiome

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Background Gut fungi are increasingly recognized as important contributors to host physiology, although most studies have focused on gut bacteria. Post-translational modifications (PTMs) of proteins play vital roles in cell metabolism. However, the contribution of gut fungi to host protein PTMs remains unclear. Mining gut fungi that mediate host protein PTMs and dissecting their mechanism are urgently needed. Results We studied the gut fungal communities of 56 weaned piglets and 56 finishing pigs from seven pig breeds using internal transcribed spacer (ITS) gene amplicon sequencing and metagenomics. The results showed that Kazachstania slooffiae was the most abundant gut fungal species in the seven breeds of weaned piglets. K. slooffiae decreased intestinal epithelial lysine succinylation levels, and these proteins were especially enriched in the glycolysis pathway. We demonstrated that K. slooffiae promoted intestinal epithelial glycolysis by decreasing lysine succinylation by activating sirtuin 5 (SIRT5). Furthermore, K. slooffiae-derived 5′-methylthioadenosine metabolite promoted the SIRT5 activity. Conclusions These findings provide a landscape of gut fungal communities of pigs and suggest that K. slooffiae plays a crucial role in intestinal glycolysis metabolism through lysine desuccinylation. Our data also suggest a potential protective strategy for pigs with an insufficient intestinal energy supply.

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Section: Resultssupporting

confidence: 82%

“…Glucose consumption, lactate production, ATP content, cAMP levels, and SIRTs activity were measured as described below. The concentrations of 5′-methylthioadenosine were chosen according to previously described procedures [ 59 , 60 ].…”

Section: Methodsmentioning

confidence: 99%

Core-predominant gut fungus Kazachstania slooffiae promotes intestinal epithelial glycolysis via lysine desuccinylation in pigs

Chen²,

Hou

et al. 2023

Microbiome

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“…Mitogen-stimulated activation of murine and human lymphocytes (9,53), lymphocyte-mediated cytolysis (56), and natural killer cellmediated cytotoxicity (10) are strongly inhibited by MTA. Although the 70Z/3 pre-B cells used in this study respond to multiple mitogens and cytokines, we focused on LPS signal transduction, which plays an important role in the murine immune response through the stimulation of B-lymphocyte proliferation (16) and macrophage activation (21).…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions.

Law¹,

Stimmel²,

Damore³

et al. 1992

Mol. Cell. Biol.

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We show that both the lipopolysaccharide (LPS)-induced activation of NF-cB DNA binding and K gene expression are blocked by treating murine pre-B lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhibitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of membrane polypeptides is also inhibited by MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-KcB and c gene activation in LPS-treated 70Z/3 cells is blocked by mevinolin, an inhibitor that prevents protein isoprenylation. Interestingly, mevinolin-treated cells also exhibited a marked reduction in the methylation of membrane proteins. Neither MTA nor mevinolin significantly inhibited NF-KB activation by phorbol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carboxyl methylated and/or isoprenylated proteins play an essential role in the LPS-signaling pathway.

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Methylthioadenosine

Schlenk

1983

Advances in Enzymology - And Related Areas of Molecular Biology

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Inhibition of lymphocyte cyclic AMP phosphodiesterase and lymphocyte function by 5′-methylthioadenosine

Cited by 13 publications

References 18 publications

Core-predominant gut fungus Kazachstania slooffiae promotes intestinal epithelial glycolysis via lysine desuccinylation in pigs

Core-predominant gut fungus Kazachstania slooffiae promotes intestinal epithelial glycolysis via lysine desuccinylation in pigs

Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions.

Methylthioadenosine

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