scholarly journals Blood Pressure–Lowering by the Antioxidant Resveratrol Is Counterintuitively Mediated by Oxidation of cGMP-Dependent Protein Kinase

Circulation ◽  
2019 ◽  
Vol 140 (2) ◽  
pp. 126-137 ◽  
Author(s):  
Oleksandra Prysyazhna ◽  
Kathryn Wolhuter ◽  
Christopher Switzer ◽  
Celio Santos ◽  
Xiaoping Yang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Protein Kinase ◽  
Blood Pressure Lowering ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Pressure Lowering ◽  
Dependent Protein

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.

cDNA Cloning and Gene Expression of Human Type Iα cGMP-Dependent Protein Kinase

Hypertension ◽  
1996 ◽  
Vol 27 (3) ◽  
pp. 552-557 ◽  
Author(s):  
Naohisa Tamura ◽  
Hiroshi Itoh ◽  
Yoshihiro Ogawa ◽  
Osamu Nakagawa ◽  
Masaki Harada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cdna Cloning ◽  
Dependent Protein Kinase ◽  
Human Type ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

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.

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