2‐5A‐dependent endoribonuclease activity and effects of A2'p5'A2'p5'A (2‐5A core) in mouse pancreatic islets

Rhodes, Christopher J.; Taylor, K. W.

doi:10.1016/0014-5793(85)80233-7

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…The cells were cultured for a further 24 h. At near confiuency (-2-4 x 10 G cells per dish), the cells were trypsinized and washed three times in phosphate buffered saline by centrifugation at 4°C, and the cell pellet was homogenized in NP40. Protein concentration was determined as described previously (12). Immunohistochemistry using specific antibodies against insulin or glucagon showed that 63% of aTC3 cells were glucagon positive and none were insulin positive.…”

Section: Methodsmentioning

confidence: 99%

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Differential Responsiveness to Interferon-α in β-Cells and Non-β-Cells

Bonnevie‐Nielsen¹,

Buschard²,

Dyrberg

1996

Diabetes

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Interferon-alpha (IFN-alpha) is important in the innate immune defense, particularly in viral infections. IFN-alpha induces 2',5'A synthetase, the products of which, 2',5'-oligoadenine nucleotides, activate mRNA degrading enzymes. IFN-alpha is the first detectable cytokine in the insulitis lesion seen in recent-onset IDDM, and insulin promoter directed expression of IFN-alpha in transgenic mice leads to development of IDDM. Here, we demonstrate that IFN-alpha induces 2',5'A synthetase activity only in insulin-producing betaTC3 cells and in isolated single rat beta-cells but not in alphaTC3 cells or in isolated rat non-beta-cells. The increased responsiveness of beta-cells but not non-beta-cells to IFN-alpha with the ensuing activation of the mRNA-degrading 2',5'A synthetase system suggests why only the beta-cells are destroyed in the diabetogenic process.

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Section: Methodsmentioning

confidence: 99%

“…that uses ATP in generating 2',5'-oligoadenylates (2',5'A), which in turn serve as substrate for a latent endoribonuclease (RNaseL) (10). The outcome is an inhibition of virus replication and cellular protein synthesis (11,12).…”

mentioning

confidence: 99%

Differential Responsiveness to Interferon-α in β-Cells and Non-β-Cells

Bonnevie‐Nielsen¹,

Buschard²,

Dyrberg

1996

Diabetes

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show abstract

“…Interferon has been shown to inhibit insulin biosynthesis selectively [35]. Furthermore, interferon induces latent 2'-5'oligoadenylate-dependent ribonuclease activity in islets [36]. In the presence of 2'-5'-oligoadenylates, this ribonuclease cleaves mRNA, rRNA and single-stranded viral RNA [37].…”

Section: Light Microscopy Studiesmentioning

confidence: 99%

Effects of a diabetogenic strain of encephalomyocarditis (EMC) virus on protein synthesis in mouse islets of Langerhans

Ward

Clemens

Taylor

1990

Biochemical Journal

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The effects of a diabetogenic strain of encephalomyocarditis (EMC) virus on total protein and insulin biosynthesis in mouse islets of Langerhans have been studied in tissue culture. In dispersed mouse islets, the rates of protein biosynthesis were assessed by measuring the incorporation of [3H]leucine into proteins. In infected dispersed islets incubated in 20 mM-glucose, both insulin and total protein biosynthesis were decreased at 6 h; only insulin biosynthesis was significantly decreased at 3 h. In whole islets, EMC virus brought about a decrease in glucose-stimulated protein and insulin biosynthesis as early as 2 h after infection without concomitant effects on insulin release. This inhibition of protein biosynthesis was still apparent at 20 h post-infection, at which time insulin release was found to be markedly elevated, and the islet insulin content was moderately decreased. At 44 h post-infection, glucose-induced insulin biosynthesis was preferentially inhibited. Infected islets at this later time point also displayed elevated levels of insulin release, and a marked loss of islet insulin content. When insulin mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were assessed by dot-blot hybridization using appropriate cDNA probes, levels of insulin mRNA were shown to decrease steadily during the first 20 h of infection, in contrast with the levels of GAPDH mRNA. At 44 h post-infection, both types of mRNA were markedly decreased. It is suggested that there is an initial early 'shut-off' of protein synthesis without other detectable changes in islet function. This is followed by a phase where both insulin mRNA levels and insulin synthesis are dramatically decreased.

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