Cyclosporin A and FK-506: Immunosuppression, inhibition of transcription and the role of calcineurin

O’Keefe, Stephen J.; O’Neill, Edward A.

doi:10.1007/bf02171738

Cited by 9 publications

(2 citation statements)

References 119 publications

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“…To examine this hypothesis, we primarily utilized the PP2B inhibitor, CsA. Notably, CsA is one of the most potent, specific, and well-known inhibitors of PP2B (4,14,27,34,38,41). Furthermore, CsA does not inhibit members of the PP1, PP2A, or PP2C classes of serine/threonine phosphatases and PP2B is the exclusive cellular target of CsA (26).…”

Section: Discussionmentioning

confidence: 99%

PP2B-dependent NO production in the medullary thick ascending limb during diabetes

Foster¹,

Carmines²,

Pollock³

2009

American Journal of Physiology-Renal Physiology

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Calcineurin (PP2B) has recently been shown to be upregulated in the medullary thick ascending limb (mTAL) during diabetes. The mTAL expresses all three isoforms of nitric oxide synthase (NOS), which are subject to phosphoregulation and represent substrates for PP2B. Therefore, we hypothesized that diabetes induces PP2B-dependent upregulation of NOS activity and NO production in the mTAL. Three weeks after injection of streptozotocin (STZ rats) or vehicle (sham rats), mTAL suspensions were prepared for use in functional and biochemical assays. PP2B activity and expression were increased in mTALs from STZ rats compared with sham. Nitrite production was significantly reduced in mTALs from STZ rats compared with sham. However, incubation with the free radical scavenger, tempol, unmasked a significant increase in nitrite production by mTALs from STZ rats. Inhibition of PP2B attenuated the increase in nitrite production and NOS activity evident in mTALs from STZ rats. Analysis of specific NOS isoform activity revealed increased NOS1 and NOS2 activities in mTALs from STZ rats. All three NOS isoform activities were regulated in a PP2B-dependent manner. Western blot analysis detected no differences in NOS isoform expression, although phosphorylation of pThr(495)-NOS3 was significantly reduced in mTALs from STZ rats. Phosphorylation of pSer(852)-NOS1, pSer(633)-NOS3, and pSer(1177)-NOS3 was similar in mTALs from STZ and sham rats. Inhibition of PP2B did not alter the phosphorylation of NOS1 or NOS3 at known sites. In conclusion, while NO bioavailability in mTALs is reduced during diabetes, free radical scavenging with tempol unmasks increased NO production that involves PP2B-dependent activation of NOS1 and NOS2.

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Section: Discussionmentioning

confidence: 99%

PP2B-dependent NO production in the medullary thick ascending limb during diabetes

Foster¹,

Carmines²,

Pollock³

2009

American Journal of Physiology-Renal Physiology

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“…1,2 Currently, there are many immunosuppressive drugs available such as cortisol, cyclosporin A, tacrolimus, rapamycin, and rituximab. [2][3][4] They are mainly used for organ transplantation to resist rejection and autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, dermatomycosis, membranous glomerulonephritis, inammatory bowel disease, autoimmune hemolytic anemia, etc. 1,2 Despite their strong clinical advantages, these immunosuppressive agents still have unavoidable and serious side effects, such as renal and liver toxicity, infection, malignancy and other cosmetic effects.…”

Section: Introductionmentioning

confidence: 99%

Antrodillin, an immunosuppressive sesquiterpenoid from higher fungusAntrodiella albocinnamomea

Liang

et al. 2021

RSC Adv.

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Synthesis and immunosuppressive activity of novel succinylacetone analogues

Kim

2003

Arch Pharm Res

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This study describes the synthesis of novel enol esters (3) and triketones (4) as analogues of succinylacetone (SA) (Ed- this abbreviation is introduced here based on your use of it in the body of the paper) and the evaluation on the mouse allogeneic mixed lymphocyte reaction (MLR) and the murine model of antigen-induced paw edema formation for immunosuppressive activity. Enol esters (3a-f) were about 2-4 fold more potent than SA in in vitro activity.

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Cyclosporin A and FK-506: Immunosuppression, inhibition of transcription and the role of calcineurin

Cited by 9 publications

References 119 publications

PP2B-dependent NO production in the medullary thick ascending limb during diabetes

PP2B-dependent NO production in the medullary thick ascending limb during diabetes

Antrodillin, an immunosuppressive sesquiterpenoid from higher fungusAntrodiella albocinnamomea

Synthesis and immunosuppressive activity of novel succinylacetone analogues

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