Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells

Regan, Jacob T C; Mirczuk, Samantha; Scudder, Christopher; Stacey, Emily; Khan, Sabah; Worwood, Michael; Powles, Torinn; Dennis-Beron, J Sebastian; Ginley-Hidinger, Matthew; McGonnell, Imelda M.; Volk, Holger A.; Strickland, Rhiannon; Tivers, Michael; Lipscomb, Victoria

doi:10.3390/cells10020398

Cited by 6 publications

(7 citation statements)

References 92 publications

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“…GC-B has a critical role in the bifurcation of axons during development ( Schmidt et al, 2018 ) extending previous observations that the natriuretic peptide systems play roles in regulating neural development ( DiCicco-Bloom et al, 2004 ; Müller et al, 2009 ). Collectively, these findings support the notion that CNP is a prominent regulatory factor in the nervous system ( Kuhn, 2016 ; Regan et al, 2021 ).…”

Section: Discussionsupporting

confidence: 83%

Retinal degeneration protein 3 controls membrane guanylate cyclase activities in brain tissue

Chen

Bräuer

Koch

2022

Front. Mol. Neurosci.

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The retinal degeneration protein RD3 is involved in regulatory processes of photoreceptor cells. Among its main functions is the inhibition of photoreceptor specific membrane guanylate cyclases during trafficking from the inner segment to their final destination in the outer segment. However, any physiological role of RD3 in non-retinal tissue is unsolved at present and specific protein targets outside of retinal tissue have not been identified so far. The family of membrane bound guanylate cyclases share a high homology of their amino acid sequences in their cytoplasmic domains. Therefore, we reasoned that membrane guanylate cyclases that are activated by natriuretic peptides are also regulated by RD3. We analyzed transcript levels of the rd3 gene and natriuretic peptide receptor genes Npr1 and Npr2 in the mouse retina, cerebellum, hippocampus, neocortex, and the olfactory bulb during development from the embryonic to the postnatal stage at P60. The rd3 gene showed a lower expression level than Npr1 and Npr2 (encoding for GC-A and GC-B, respectively) in all tested brain tissues, but was at least one order of magnitude higher in the retina. RD3 and natriuretic peptide receptor GCs co-express in the retina and brain tissue leading to functional tests. We expressed GC-A and GC-B in HEK293T cells and measured the inhibition of GCs by RD3 after activation by natriuretic peptides yielding inhibitory constants around 25 nM. Furthermore, endogenous GCs in astrocytes were inhibited by RD3 to a similar extent. We here show for the first time that RD3 can inhibit two hormone-stimulated GCs, namely GC-A and GC-B indicating a new regulatory feature of these hormone receptors.

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Section: Discussionsupporting

confidence: 83%

Retinal degeneration protein 3 controls membrane guanylate cyclase activities in brain tissue

Chen

Bräuer

Koch

2022

Front. Mol. Neurosci.

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“…CNP is now regarded as an autocrine/paracrine regulator with broad expression in the body [ 23 ]. CNP produces a series of biological effects by the cGMP signaling pathway through binding to its specific natriuretic peptide receptor B (NPR-B) [ 24 , 25 ], such as regulation of the proliferation of myocardial cells [ 26 ]; maintaining cardiovascular homeostasis [ 27 ]; inhibition of bone growth and cartilage development [ 28 ]; promote follicular development [ 29 ]. Our group’s previous studies have already shown that CNP can induce sperm capacitation in normal people through cGMP [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

C-Type Natriuretic Peptide (CNP) Could Improve Sperm Motility and Reproductive Function of Asthenozoospermia

Dong

et al. 2022

IJMS

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This study is to analyze the effect of C-type natriuretic peptide (CNP) on sperm motility of asthenozoospermia and explore the influence mechanism of CNP on the reproductive system and sperm motility. Our results showed that the concentration of CNP in asthenospermia patients’ semen was lower than in normal people’s. The motility of sperm could be improved markedly by CNP and 8-Br-cGMP, while the effect of CNP was inhibited by NPR-B antagonist and KT5823. In the asthenozoospermia mouse model induced by CTX, CNP injection could improve sperm motility in the epididymis, alleviate tissue damage in the testes and epididymis, and increase testosterone levels. The asthenospermia mouse model showed high activity of MDA and proinflammatory factors (TNF-α, IL-6), as well as low expression of antioxidants (SOD, GSH-Px, CAT) in the testis and epididymis, but this situation could be significantly ameliorated after being treated with CNP. Those studies indicated that the concentration of CNP in the semen of asthenospermia patients is lower than in normal people and could significantly promote sperm motility through the NPR-B/cGMP pathway. In the asthenospermia mouse model induced by CTX, CNP can alleviate the damage of cyclophosphamide to the reproductive system and sperm motility. The mechanism may involve increasing testosterone and reducing ROS and proinflammatory factors to damage the tissue and sperm.

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“…We hypothesized that AMPK is crucial for the adaptive properties of astrocytes upon cellular insult; hence, we sought to further characterize the involvement of AMPK in the control of astrocytic functions, and in particular, the regulation of glutamate uptake. We therefore used the C6 astrocytoma cell line [ 35 ], as a reliable astrocyte-like cell model that has been used for decades to study astrocyte biology [ 36 , 37 , 38 ]. We genetically modified this cell line to allow manipulation of AMPK activity through the overexpression of a dominant negative AMPKα 1 isoform.…”

Section: Introductionmentioning

confidence: 99%

AMPK Modulates the Metabolic Adaptation of C6 Glioma Cells in Glucose-Deprived Conditions without Affecting Glutamate Transport

Nascimento

Verfaillie

Ates

et al. 2022

Cells

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Energy homeostasis in the central nervous system largely depends on astrocytes, which provide metabolic support and protection to neurons. Astrocytes also ensure the clearance of extracellular glutamate through high-affinity transporters, which indirectly consume ATP. Considering the role of the AMP-activated protein kinase (AMPK) in the control of cell metabolism, we have examined its implication in the adaptation of astrocyte functions in response to a metabolic stress triggered by glucose deprivation. We genetically modified the astrocyte-like C6 cell line to silence AMPK activity by overexpressing a dominant negative mutant of its catalytic subunit. Upon glucose deprivation, we found that C6 cells maintain stable ATP levels and glutamate uptake capacity, highlighting their resilience during metabolic stress. In the same conditions, cells with silenced AMPK activity showed a reduction in motility, metabolic activity, and ATP levels, indicating that their adaptation to stress is compromised. The rate of ATP production remained, however, unchanged by AMPK silencing, suggesting that AMPK mostly influences energy consumption during stress conditions in these cells. Neither AMPK modulation nor prolonged glucose deprivation impaired glutamate uptake. Together, these results indicate that AMPK contributes to the adaptation of astrocyte metabolism triggered by metabolic stress, but not to the regulation of glutamate transport.

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Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells

Cited by 6 publications

References 92 publications

Retinal degeneration protein 3 controls membrane guanylate cyclase activities in brain tissue

Retinal degeneration protein 3 controls membrane guanylate cyclase activities in brain tissue

C-Type Natriuretic Peptide (CNP) Could Improve Sperm Motility and Reproductive Function of Asthenozoospermia

AMPK Modulates the Metabolic Adaptation of C6 Glioma Cells in Glucose-Deprived Conditions without Affecting Glutamate Transport

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