Specific expression of soluble adenylyl cyclase in male germ cells

Sinclair, Meeghan L.; Wang, Xiang-Yuan; Mattia, Melissa; Conti, Marco; Buck, Jochen; Wolgemuth, Debra J.; Levin, Lonny R.

doi:10.1002/(sici)1098-2795(200005)56:1<6::aid-mrd2>3.0.co;2-m

Cited by 105 publications

(17 citation statements)

References 29 publications

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“…Similar results were found in human neutrophils treated with ionomycin [60]. sAC was initially characterized in mammalian sperm, but is now known to be expressed in a variety of tissues including brain, liver, heart, spleen, epithelial cells and neutrophils [21, 60]. In addition to regulating sperm function, sAC is implicated in mediating neuronal differentiation and fast migration [25, 61], tumor necrosis factor (TNF) signal transduction to inhibit TNF induced hydrogen peroxide release [60], and regulation of ciliary beat frequency in the airway [62].…”

Section: Discussionsupporting

confidence: 69%

Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms

Salinthone

Schillace

Tsang

et al. 2011

The Journal of Nutritional Biochemistry

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Lipoic acid (LA) is a naturally occurring fatty acid that exhibits anti-oxidant and antiinflammatory properties and is being pursued as a therapeutic for many diseases including multiple sclerosis, diabetic polyneuropathy and Alzheimer's disease. We previously reported on the novel finding that racemic LA (50:50 mixture of R and S LA) stimulates cAMP production, activates prostanoid EP2 and EP4 receptors and adenylyl cyclases (AC), and suppresses activation and cytotoxicity in NK cells. In this study we present evidence that furthers our understanding of the mechanisms of action of LA. Using various LA derivatives, dihydrolipoic acid (DHLA), S,Sdimethyl lipoic acid (DMLA) and lipoamide (LPM), we discovered that only LA is capable of stimulating cAMP production in NK cells. Furthermore, there is no difference in cAMP production after stimulation with either R-LA, S-LA or racemic LA. Competition and synergistic studies indicate that LA may also activate AC independent of the EP2 and EP4 receptors. Pretreatment of PBMCc with KH7 (a specific peptide inhibitor of soluble AC) and the calcium inhibitor (Bapta) prior to LA treatment resulted in reduced cAMP levels, suggesting that soluble AC and calcium signaling mediate LA stimulation of cAMP production. In addition, pharmacological inhibitor studies demonstrate that LA also activates other G-protein coupled receptors, including histamine and adenosine, but not the beta adrenergic receptors. These novel findings provide information to better understand the mechanisms of action of LA, which can help facilitate the use of LA as a therapeutic for various diseases.

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Section: Discussionsupporting

confidence: 69%

Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms

Salinthone

Schillace

Tsang

et al. 2011

The Journal of Nutritional Biochemistry

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“…Expression of sAC mRNA in mice is first detectable in mid-pachytene spermatocyte in meiotic prophase and becomes much more abundant in round spermatids (Sinclair et al, 2000). Similarly, Mn 2+ -sensitive adenylyl cyclase activity (Braun and Dods, 1975) and full-length sAC (Xie and Conti, 2004), are detected first in testis homogenate from rats aged 20–25 days, corresponding to the secondary spermatocyte stage.…”

Section: Sac Is Indispensable In Spermatogenesis and Fertilizationmentioning

confidence: 99%

“…The adenylyl cyclase activity and protein expression level of sAC increase further and plateau as the sperms become mature. Northern blot analysis of poly-A + mRNA from preparations of adult mouse testis reveals that the sAC activity originate from germ cells but not Sertoli or Leydig cells (Sinclair et al, 2000). Although mRNA of sAC is detectable by RT-PCR in ovarian preparations, Northern blot and in situ hybridization reveal only background staining, which implies that the high abundance of sAC expression is not a general phenomenon for all germ cells but specific for males (Sinclair et al, 2000).…”

Section: Sac Is Indispensable In Spermatogenesis and Fertilizationmentioning

confidence: 99%

Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation

Chang

Oude-Elferink

2014

Front. Physiol.

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The evolutionarily conserved soluble adenylyl cyclase (sAC, adcy10) was recently identified as a unique source of cAMP in the cytoplasm and the nucleus. Its activity is regulated by bicarbonate and fine-tuned by calcium. As such, and in conjunction with carbonic anhydrase (CA), sAC constitutes an HCO−3/CO−2/pH sensor. In both alpha-intercalated cells of the collecting duct and the clear cells of the epididymis, sAC is expressed at significant level and involved in pH homeostasis via apical recruitment of vacuolar H+-ATPase (VHA) in a PKA-dependent manner. In addition to maintenance of pH homeostasis, sAC is also involved in metabolic regulation such as coupling of Krebs cycle to oxidative phosphorylation via bicarbonate/CO2 sensing. Additionally, sAC also regulates CFTR channel and plays an important role in regulation of barrier function and apoptosis. These observations suggest that sAC, via bicarbonate-sensing, plays an important role in maintaining homeostatic status of cells against fluctuations in their microenvironment.

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“…sAC is found in almost every mammalian tissue [62,64,86–88], including neurons [89]. Within the cell, sAC localization and activity are found in mitochondria, nuclei, and cytoplasmic compartments including in axons, dendrites and growth cones (Fig.…”

Section: Soluble Adenylyl Cyclasementioning

confidence: 99%

The role of soluble adenylyl cyclase in neurite outgrowth

Stiles

Kapiloff

Goldberg

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Axon regeneration in the mature central nervous system is limited by extrinsic inhibitory signals and a postnatal decline in neurons' intrinsic growth capacity. Neuronal levels of the second messenger cAMP are important in regulating both intrinsic growth capacity and neurons' responses to extrinsic factors. Approaches which increase intracellular cAMP in neurons enhance neurite outgrowth and facilitate regeneration after injury. Thus, understanding the factors which affect cAMP in neurons is of potential therapeutic importance. Recently, soluble adenylyl cyclase (sAC, ADCY10), the ubiquitous, non-transmembrane adenylyl cyclase, was found to play a key role in neuronal survival and axon growth. sAC is activated by bicarbonate and cations and may translate physiologic signals from metabolism and electrical activity into a neuron's decision to survive or regenerate. Here we critically review the literature surrounding sAC and cAMP signaling in neurons to further elucidate the potential role of sAC signaling in neurite outgrowth and regeneration.

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Specific expression of soluble adenylyl cyclase in male germ cells

Cited by 105 publications

References 29 publications

Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms

Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms

Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation

The role of soluble adenylyl cyclase in neurite outgrowth

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