scholarly journals The Role of cAMP-PKA Pathway in Lactate-Induced Intramuscular Triglyceride Accumulation and Mitochondria Content Increase in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Siyu Chen ◽  
Lei Zhou ◽  
Jingquan Sun ◽  
Yaqian Qu ◽  
Min Chen

The glycolytic product of exercise, lactate, has long been recognized to promote lipid accumulation by activation of G-protein-coupled receptor 81 (GPR81) and inhibition of the cyclic adenosine monophosphate-protein kinase A (cAMP –PKA) pathway in adipose tissue. Whether lactate causes a similar process in skeletal muscle is unclear. Lactate might also improve mitochondria content in skeletal muscle; however, the mechanism is not clarified either. In this study, using intramuscular injection of lactate to the gastrocnemius and intraperitoneal injection of forskolin (activator of cAMP-PKA pathway), we identified the role of the cAMP-PKA pathway in lactate-induced intramuscular triglyceride accumulation and mitochondrial content increase. The intramuscular triglyceride level in the gastrocnemius increased after 5weeks of lactate injection (p<0.05), and this effect was blocked by forskolin injection (p<0.05). Corresponding expression level changes of GPR81, P-PKA/PKA, P-CREB/cAMP-response element binding protein (CREB), and proteins related to lipid metabolism suggest that lactate could induce intramuscular triglyceride accumulation partly through the inhibition of the cAMP-PKA pathway. Meanwhile, the intramuscular expression of citrate synthase (CS) and the activity of CS increased after 5weeks of lactate injection (p<0.05), but the change of CS expression was not blocked by forskolin injection, suggesting other mechanisms might exist. Consequently, exploration for other potential mechanisms that might contribute to the lactate-induced mitochondria content increase was conducted. We found an increase in the contents of lactate-related metabolites in skeletal muscle mitochondria after acute lactate injection (the p-value of each analysis is less than 0.05). LHDA was also validated to exist in mitochondria in this study. These results provide a possibility for metabolism-related mechanisms of lactate-induced mitochondria content increase. Future study is needed to validate this hypothesis. In conclusion, lactate-induced intramuscular triglyceride accumulation is achieved by inhibition of lipolysis, and this process is regulated by the cAMP-PKA pathway. Promoted lipogenesis also contributes to lactate-induced triglyceride accumulation, and this process might also be regulated by the cAMP-PKA pathway. Lactate injection might increase mitochondria content and cAMP-PKA pathway might have a limited contribution, while other metabolism-related mechanisms might play a prominent role.

2020 ◽  
Vol 3 (11) ◽  
pp. 1100-1104
Author(s):  
Hussein Naeem Aldhaheri ◽  
Ihsan Edan AlSaimary ◽  
Murtadha Mohammed ALMusafer

      The Aim of this study was to determine Immunogenetic expression of  Toll-like receptor gene clusters related to prostatitis, to give acknowledge about Role of TLR in prostatitis immunity in men from Basrah and Maysan provinces. A case–control study included 135 confirmed prostatitis patients And 50 persons as a control group. Data about age, marital status, working, infertility, family history and personal information like (Infection, Allergy, Steroid therapy, Residency, Smoking, Alcohol Drinking, Blood group, Body max index (BMI) and the clinical finding for all patients of Prostatitis were collected. This study shows the effect of PSA level in patients with prostatitis and control group, with P-value <0.0001 therefore the study shows a positive significant between elevated PSA levels and Prostatitis.


2019 ◽  
Author(s):  
Bella Grigorenko ◽  
Igor Polyakov ◽  
Alexander Nemukhin

<p>We report a mechanism of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) conversion by the mammalian type V adenylyl cyclase revealed in molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) simulations. We characterize a set of computationally derived enzyme-substrate (ES) structures showing an important role of coordination shells of magnesium ions in the solvent accessible active site. Several stable six-fold coordination shells of Mg<sub>A</sub><sup>2+ </sup>are observed in MD simulations of ES complexes. In the lowest energy ES conformation, the coordination shell of Mg<sub>A</sub><sup>2+ </sup>does not include the O<sub>δ1</sub> atom of the conserved Asp440 residue. Starting from this conformation, a one-step reaction mechanism is characterized which includes proton transfer from the ribose O<sup>3'</sup>H<sup>3' </sup>group in ATP to Asp440 via a shuttling water molecule and P<sup>A</sup>-O<sup>3A</sup> bond cleavage and O<sup>3'</sup>-P<sup>A</sup> bond formation. The energy profile of this route is consistent with the observed reaction kinetics. In a higher energy ES conformation, Mg<sub>A</sub><sup>2+</sup> is bound to the O<sub>δ1</sub>(Asp440) atom as suggested in the relevant crystal structure of the protein with a substrate analog. The computed energy profile initiated by this ES is characterized by higher energy expenses to complete the reaction. Consistently with experimental data, we show that the Asp440Ala mutant of the enzyme should exhibit a reduced but retained activity. All considered reaction pathways include proton wires from the O<sup>3'</sup>H<sup>3' </sup>group via shuttling water molecules. </p>


Author(s):  
Bruno Rocha de Avila Pelozin ◽  
◽  
Larissa Ferreira-Santos ◽  
Luis Felipe Rodrigues ◽  
Edilamar Menezes de Oliveira ◽  
...  

2018 ◽  
Vol 9 (02) ◽  
pp. 192
Author(s):  
Wiwid Wahyuningsih ◽  
Atik Setiyaningsih

ABSTRAKLatar Belakang : Keberadaan kader di posyandu sebagai salah satu sistem penyelenggarakan pelayanan sangat dibutuhkan. Mereka adalah ujung tombak  pelayanan kesehatan yang merupakan kepanjangtanganan puskesmas Jawa Tengah tahun 2011 jumlah gizi kurang 5,35% dan gizi buruk 0,10%. Untuk Kabupaten Semarang dari 23.562 balita yang ditimbang pada tahun 2011 gizi lebih 1,13%, gizi baik 93,51%, gizi kurang 4,86% dan gizi buruk 0,49% (DepKes Prov Jateng, 2011). Tujuan Penelitian : Penelitian ini bertujuan untuk mengetahui hubungan peran kader posyandu dengan status gizi balita. Metode Penelitian : Desain penelitian ini adalah survey analitik dengan menggunakan pendekatan cross sectional. Populasi dalam penelitian ini adalah seluruh balita di Posyandu Mawar di Desa Gedangan sejumlah 40 responden, dengan teknik total sampling dan analisa data chi square. Hasil Penelitian : Hasil perhitungan chi square di peroleh X² hitung 10.644 pada df=4, P.value 0.031 dimana probabilitas lebih kecil dari level of significant 5 % (0,001 < 0,05) berarti Ha diterima dan Ho ditolak. Kesimpulan : ada hubungan antara peran kader posyandu dengan status gizi pada balita.Kata Kunci : peran kader , status gizi balitaCADERE ROLE RELATIONSHIP WITH NUTRITIONAL STATUS OF CHILDREN POSYANDUABSTRACTBackground : posyandu cadre in Existence as one of the 56th's service system is urgently needed. They are the tip of the Spear is a kepanjangtanganan health services clinics in Central Java in 2011 the amount of nutrition less 5.35% 0.10% and malnutrition. To Semarang from 23.562 toddler who weighed in 2011 more nutritional 1.13%, 93,51%, good nutrition nutrition less 4.86% and 0.49% poor nutrition (Department of Health Central Java Prov., 2011). Objective : the research aims to find out the relationship role of posyandu cadre with the nutritional status of children. Methods : the design of this research is a survey using the analytic approach of cross sectional. The population in this study are all the toddlers at the Rose in the village of Posyandu Gedangan some 38 respondents, with total sample techniques and data analysis a chi square. The results :. The chi square calculation results in getting X ² count 10.644 on df = 4, P. value 0.031 where probability is smaller than the level of significant 5% (0.001 < 0.05) mean Ha Ho accepted and rejected. Conclusion : there is a connection between the role of cadres of posyandu with nutritional status on toddlers.Keywords : the role of cadres, toddler nutrition status


2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  

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