scholarly journals The Foraging Gene, a New Environmental Adaptation Player Involved in Xenobiotic Detoxification

2021 ◽  
Vol 18 (14) ◽  
pp. 7508
Author(s):  
Marcel Amichot ◽  
Sophie Tarès
Keyword(s):  
Cytochrome P450 ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Detoxification Enzymes ◽  
Dependent Protein Kinase ◽  
Xenobiotic Detoxification ◽  
Cgmp Dependent Protein Kinase ◽  
Foraging Gene ◽  
Dependent Protein ◽  
Low Levels

Foraging is vital for animals, especially for food. In Drosophila melanogaster, this behavior is controlled by the foraging gene (for) which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). In wild populations of Drosophila, rover individuals that exhibit long foraging trails and sitter individuals that exhibit short ones coexist and are characterized by high and low levels of PKG activity, respectively. We, therefore, postulated that rover flies are more exposed to environmental stresses, including xenobiotics contamination, than sitter flies. We then tested whether these flies differed in their ability to cope with xenobiotics by exposing them to insecticides from different chemical families. We performed toxicological tests and measured the activity and expression levels of different classes of detoxification enzymes. We have shown that a link exists between the for gene and certain cytochrome P450-dependent activities and that the expression of the insecticide-metabolizing cytochrome P450 Cyp6a2 is controlled by the for gene. An unsuspected regulatory pathway of P450s expression involving the for gene in Drosophila is revealed and we demonstrate its involvement in adaptation to chemicals in the environment. This work can serve as a basis for reconsidering adaptation to xenobiotics in light of the behavior of species, including humans.

scholarly journals The cGMP-Dependent Protein Kinase 2 Contributes to Cone Photoreceptor Degeneration in the Cnga3-Deficient Mouse Model of Achromatopsia

2020 ◽  
Vol 22 (1) ◽  
pp. 52
Author(s):  
Mirja Koch ◽  
Constanze Scheel ◽  
Hongwei Ma ◽  
Fan Yang ◽  
Michael Stadlmeier ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mouse Model ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cone Photoreceptor ◽  
Photoreceptor Degeneration ◽  
Dependent Protein Kinase ◽  
Genetic Ablation ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

Mutations in the CNGA3 gene, which encodes the A subunit of the cyclic guanosine monophosphate (cGMP)-gated cation channel in cone photoreceptor outer segments, cause total colour blindness, also referred to as achromatopsia. Cones lacking this channel protein are non-functional, accumulate high levels of the second messenger cGMP and degenerate over time after induction of ER stress. The cell death mechanisms that lead to loss of affected cones are only partially understood. Here, we explored the disease mechanisms in the Cnga3 knockout (KO) mouse model of achromatopsia. We found that another important effector of cGMP, the cGMP-dependent protein kinase 2 (Prkg2) is crucially involved in cGMP cytotoxicity of cones in Cnga3 KO mice. Virus-mediated knockdown or genetic ablation of Prkg2 in Cnga3 KO mice counteracted degeneration and preserved the number of cones. Analysis of markers of endoplasmic reticulum stress and unfolded protein response confirmed that induction of these processes in Cnga3 KO cones also depends on Prkg2. In conclusion, we identified Prkg2 as a novel key mediator of cone photoreceptor degeneration in achromatopsia. Our data suggest that this cGMP mediator could be a novel pharmacological target for future neuroprotective therapies.

scholarly journals Cyclic Guanosine Monophosphate-dependent Protein Kinase I Promotes Adhesion of Primary Vascular Smooth Muscle Cells

2008 ◽  
Vol 19 (10) ◽  
pp. 4434-4441 ◽  
Author(s):  
Pascal Weinmeister ◽  
Robert Lukowski ◽  
Stefan Linder ◽  
Claudia Traidl-Hoffmann ◽  
Ludger Hengst ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Adhesion ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Protein Kinase ◽  
Dependent Protein

The cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI) pathway regulates many cellular functions. The current study shows that 8-Br-cGMP stimulates the number of attached primary but not that of subcultured murine vascular smooth muscle cells (VSMCs). These effects of 8-Br-cGMP require the presence of cGKI. In agreement with previous studies, cGKI inhibited the number of cells in repeatedly passaged murine VSMCs. Activation of the cGMP/cGKI pathway in freshly isolated primary VSMCs slightly decreased apoptosis and strongly increased cell adhesion. The stimulation of cell adhesion by cGKI involves an inhibition of the RhoA/Rho kinase pathway and increased exposure of β1 and β3 integrins on the cell surface. Together, these results identify a novel proadhesive function of cGMP/cGKI signaling in primary VSMCs and suggest that the opposing effects of this pathway on VSMC number depend on the phenotypic context of the cells.

Intrathecally Administered cGMP-dependent Protein Kinase Iα Inhibitor Significantly Reduced the Threshold for Isoflurane Anesthesia

2000 ◽  
Vol 92 (2) ◽  
pp. 493-493 ◽  
Author(s):  
Yuan-Xiang Tao ◽  
Aalya Hassan ◽  
Roger A. Johns
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Protein Kinase ◽  
Guanosine Monophosphate ◽  
Dependent Protein Kinase ◽  
No Donor ◽  
Cgmp Dependent Protein Kinase ◽  
Significant Reversal ◽  
Cgmp Pathway ◽  
Dependent Protein

Background Inhalational anesthetics have been shown to inhibit the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Previous studies indicated that inhibition of the NO-cGMP pathway decreased the level of consciousness and augmented anesthesia, analgesia, or sedation. The current study investigated the possible involvement of cGMP-dependent protein kinases (PKGs) as major effectors for the NO-cGMP pathway in the anesthetic state. Methods After initial baseline determination of the minimum alveolar concentration (MAC), a selective cGMP-dependent protein kinase Ialpha inhibitor, Rp-8-p-CPT-cGMPS, or an NO donor, (NOC-12), were injected intrathecally. Ten minutes later, MAC measurement was repeated. The rats also were evaluated for the presence of locomotor dysfunction by intrathecal administration of Rp-8-p-CPT-cGMPS and NOC-12 in conscious rats. Results Rp-8-p-CPT-cGMPS at 25, 50, 100, and 200 microg/10 microl produced a significant decrease from isoflurane control MAC of -4+/-3.1%, 16+/-4.5%, 30+/-5.0%, and 21+/-2.2%, respectively, which was not accompanied by significant changes in either blood pressure or heart rate. In contrast, NOC-12 at 100 microg/10 microl caused an increase from isoflurane control MAC of 23+/-5.8%, which was accompanied by significant decrease in blood pressure but not in heart rate. Rp-8-p-CPT-cGMPS (100 microg/10 microl) produced a significant reversal of isoflurane MAC increase induced by NOC-12 (100 microg/10 microl), which was accompanied by significant reversal of the reduction of blood pressure induced by NOC-12. Locomotor activity was not changed. Conclusions The results indicate that cGMP-dependent protein kinase Ialpha inhibitor not only markedly reduces MAC for isoflurane, but also completely blocks the NO-induced increase in isoflurane MAC, which suggests that cGMP-dependent protein kinase Ialpha may mediate the action for the NO-cGMP pathway in anesthetic mechanisms at the spinal cord level.

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