scholarly journals Tetrandrine prevents monocrotaline-induced pulmonary arterial hypertension in rats through regulation of the protein expression of inducible nitric oxide synthase and cyclic guanosine monophosphate-dependent protein kinase type 1

2016 ◽  
Vol 64 (5) ◽  
pp. 1468-1477 ◽  
Author(s):  
Xiaowu Wang ◽  
Yongchao Yang ◽  
Dongpeng Yang ◽  
Guang Tong ◽  
Shanshan Lv ◽  
...  
2014 ◽  
Vol 50 (4) ◽  
pp. 141-145 ◽  
Author(s):  
Adolfo Baloira Villar ◽  
Guillermo Pousada Fernández ◽  
Carlos Vilariño Pombo ◽  
Marta Núñez Fernández ◽  
Jose Cifrián Martínez ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Ji-Hee Kim ◽  
Ga-Young Park ◽  
Soo Young Bang ◽  
Sun Young Park ◽  
Soo-Kyung Bae ◽  
...  

Crocin is a water-soluble carotenoid pigment that is primarily used in various cuisines as a seasoning and coloring agent, as well as in traditional medicines for the treatment of edema, fever, and hepatic disorder. In this study, we demonstrated that crocin markedly induces the expression of heme oxygenase-1 (HO-1) which leads to an anti-inflammatory response. Crocin inhibited inducible nitric oxide synthase (iNOS) expression and nitric oxide production via downregulation of nuclear factor kappa B activity in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. These effects were abrogated by blocking of HO-1 expression or activity. Crocin also induced Ca2+mobilization from intracellular pools and phosphorylation of Ca2+/calmodulin-dependent protein kinase 4 (CAMK4). CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling. Moreover, crocin-mediated suppression of iNOS expression was blocked by CAMK4 inhibition. Overall, these results suggest that crocin suppresses LPS-stimulated expression of iNOS by inducing HO-1 expression via Ca2+/calmodulin-CAMK4-PI3K/Akt-Nrf2 signaling cascades. Our findings provide a novel molecular mechanism for the inhibitory effects of crocin against endotoxin-mediated inflammation.


2020 ◽  
Vol 22 (1) ◽  
pp. 52
Author(s):  
Mirja Koch ◽  
Constanze Scheel ◽  
Hongwei Ma ◽  
Fan Yang ◽  
Michael Stadlmeier ◽  
...  

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.


Life Sciences ◽  
2019 ◽  
Vol 216 ◽  
pp. 279-286 ◽  
Author(s):  
Simone Marcieli Sartoretto ◽  
Fernanda Fernandes Santos ◽  
Beatriz Pereira Costa ◽  
Graziela Scalianti Ceravolo ◽  
Rosângela Santos-Eichler ◽  
...  

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