7 Class III adenylyl cyclases: Regulation and underlying mechanisms

Emerging evidence indicates that aberrant maternal inflammation is associated with several pregnancy-related disorders such as preeclampsia, preterm birth, and intrauterine growth restriction. Sirtuin1 (SIRT1), a class III histone deacetylase, is involved in the regulation of various physiopathological processes including cellular inflammation and metabolism. However, the effect of SIRT1 on the placental proinflammatory environment remains to be elucidated. In this study, we investigated the effect of SIRT1 on lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation and its underlying mechanisms in human first-trimester trophoblasts (Sw.71 and HTR-8/SVneo cells). Treatment with LPS elevated SIRT1 expression and induced NLRP3 inflammasome activation in mouse placental tissues and human trophoblasts. Knockdown of SIRT1 enhanced LPS-induced NLRP3 inflammasome activation, inflammatory signaling, and subsequent interleukin (IL)-1β secretion. Furthermore, knockdown of NLRP3 considerably attenuated the increase of IL-1β secretion in SIRT1-knockdown cells treated with LPS. Moreover, SIRT1 inhibited LPS-induced NLRP3 inflammasome activation by reducing oxidative stress. This study revealed a novel mechanism via which SIRT1 exerts anti-inflammatory effects, suggesting that SIRT1 is a potential therapeutic target for the prevention of inflammation-associated pregnancy-related complications.

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Adenylyl Cyclase Activity of Cya1 from the Cyanobacterium Synechocystis sp. Strain PCC 6803 Is Inhibited by Bicarbonate

Journal of Bacteriology ◽

10.1128/jb.187.14.5032-5035.2005 ◽

2005 ◽

Vol 187 (14) ◽

pp. 5032-5035 ◽

Cited By ~ 9

Author(s):

Shinji Masuda ◽

Taka-aki Ono

Keyword(s):

Adenylyl Cyclase ◽

Cyclase Activity ◽

Substrate Affinity ◽

Adenylyl Cyclases ◽

Class Iii ◽

Adenylyl Cyclase Activity ◽

Synechocystis Sp ◽

Pcc 6803

ABSTRACT Bicarbonate stimulates the activities of several class III adenylyl cyclases studied to date. However, we show here that bicarbonate decreased V max and substrate affinity in Cya1, a major adenylyl cyclase in the cyanobacterium Synechocystis sp. strain PCC 6803. This indicates that manifestation of the bicarbonate responsiveness is specifically modulated in Cya1.

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A Systematic Review of Stress-Management Interventions for Multiple Sclerosis Patients

International Journal of MS Care ◽

10.7224/1537-2073.2013-034 ◽

2014 ◽

Vol 16 (3) ◽

pp. 140-144 ◽

Cited By ~ 13

Author(s):

Alison K. Reynard ◽

Amy Burleson Sullivan ◽

Alexander Rae-Grant

Keyword(s):

Multiple Sclerosis ◽

Stress Management ◽

Clinical Markers ◽

Class Iii ◽

Multicenter Studies ◽

Management Interventions ◽

Underlying Mechanisms ◽

Multiple Sclerosis Patients ◽

American Academy Of Neurology

Background: The objective of this study was to identify stress-management interventions used for people with multiple sclerosis (MS) and systematically evaluate the efficacy of these interventions. Methods: Several strategies were used to search for studies reported in articles published up to 2013. Results: Our initial search retrieved 117 publications, of which 8 met our criteria for review. Of the eight studies, one provided Class I evidence, five provided Class III evidence, and two provided Class IV evidence for the efficacy of stress-management interventions according to the evidence classification established by the American Academy of Neurology. Most studies showed positive changes in outcomes assessed; however, the range of methodological quality among the published studies made it difficult to draw conclusions. Conclusions: The promising findings for stress-management interventions highlight the need for future studies. Additional large, prospective, multicenter studies will help to define the role of stress-management interventions in the treatment and course of MS. Furthermore, including outcome measures based on biological and clinical markers of disease will prove useful in understanding potential underlying mechanisms.

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The class III adenylyl cyclases: multi-purpose signalling modules

Cellular Signalling ◽

10.1016/s0898-6568(03)00130-x ◽

2003 ◽

Vol 15 (12) ◽

pp. 1081-1089 ◽

Cited By ~ 128

Author(s):

Jürgen U. Linder ◽

Joachim E. Schultz

Keyword(s):

Adenylyl Cyclases ◽

Class Iii

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Expression, purification, crystallization and preliminary X-ray diffraction analysis of a mammalian type 10 adenylyl cyclase

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x14004014 ◽

2014 ◽

Vol 70 (4) ◽

pp. 467-469 ◽

Cited By ~ 5

Author(s):

Silke Kleinboelting ◽

Joop van den Heuvel ◽

Christian Kambach ◽

Michael Weyand ◽

Martina Leipelt ◽

...

Keyword(s):

Diffraction Analysis ◽

Catalytic Domain ◽

Direct Interaction ◽

Adenylyl Cyclases ◽

Class Iii ◽

X Ray Diffraction ◽

Data Set ◽

X Ray ◽

Cell Parameters ◽

Structure Solution

The second messenger cAMP is synthesized in mammals by ten differently regulated adenylyl cyclases (AC1–10). These ACs are grouped into nucleotidyl cyclase class III based on homologies in their catalytic domains. The catalytic domain of AC10 is unique, however, in being activated through direct interaction with calcium and bicarbonate. Here, the production, crystallization and X-ray diffraction analysis of the catalytic domain of human AC10 are described as a basis for structural studies of regulator binding sites and mechanisms. The recombinant protein had high specific AC activity, and crystals of AC10 in space groupP63diffracted to ∼2.0 Å resolution on a synchrotron beamline. A complete diffraction data set revealed unit-cell parametersa=b= 99.65,c= 98.04 Å, indicating one AC10 catalytic domain per asymmetric unit, and confirmed that the obtained crystals are suitable for structure solution and mechanistic studies.

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Substrate selection by class III adenylyl cyclases and guanylyl cyclases

IUBMB Life ◽

10.1080/15216540500415636 ◽

2005 ◽

Vol 57 (12) ◽

pp. 797-803 ◽

Cited By ~ 20

Author(s):

Jürgen Linder

Keyword(s):

Adenylyl Cyclases ◽

Substrate Selection ◽

Class Iii ◽

Guanylyl Cyclases

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SIRT1 attenuates renal fibrosis by repressing HIF-2α

Cell Death Discovery ◽

10.1038/s41420-021-00443-x ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Peipei Li ◽

Yue Liu ◽

Xiaogang Qin ◽

Kairen Chen ◽

Ruiting Wang ◽

...

Keyword(s):

Histone Deacetylases ◽

Renal Damage ◽

Hypoxia Inducible Factor ◽

Protective Role ◽

Conditional Knockout ◽

Sirtuin 1 ◽

Class Iii ◽

Gene Expressions ◽

Underlying Mechanisms ◽

Renal Fibrogenesis

AbstractSirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase belonging to class III histone deacetylases. Previous studies have shown that SIRT1 is involved in kidney physiology regulation and protects the kidney from various pathological factors. However, the underlying mechanisms behind its function have yet to be fully elucidated. In our study, we found that ablation of Sirt1 in renal interstitial cells resulted in more severe renal damage and fibrosis in unilateral ureteral obstruction (UUO) model mice. We also observed that hypoxia-inducible factor (HIF)-2α expression was increased in Sirt1 conditional knockout mice, suggesting that HIF-2α might be a substrate of SIRT1, mediating its renoprotective roles. Therefore, we bred Hif2a deficient mice and subjected them to renal trauma through UUO surgery, ultimately finding that Hif2a ablation attenuated renal fibrogenesis induced by UUO injury. Moreover, in cultured NRK-49F cells, activation of SIRT1 decreased HIF-2α and fibrotic gene expressions, and inhibition of SIRT1 stimulated HIF-2α and fibrotic gene expressions. Co-immunoprecipitation analysis revealed that SIRT1 directly interacted with and deacetylated HIF-2α. Together, our data indicate that SIRT1 plays a protective role in renal damage and fibrosis, which is likely due to inhibition of HIF-2α.

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