#grk2

[rnomics]

Cells, Vol. 8, Pages 1596: GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice

Rheumatoid arthritis (RA) is characterized by the massive infiltration of various chronic inflammatory cells in synovia. In synovial fluid of patients with RA, M1 macrophages are dominant among all subtypes of macrophages, the mechanisms of macrophages polarization imbalance in RA has not been fully illuminated. The prostaglandin E2 (PGE2) augments M2 polarization in part via the cyclic adenosine monophosphate (cAMP)-cyclic AMP responsive element binding (CREB) signaling. However, previous study found constant stimulus of PGE2 on fibroblast-like synovial cells of adjuvant arthritis rats induced the decrease of cAMP, which is primarily caused by G protein-coupled receptor kinase 2 (GRK2)-induced EP4 over- desensitization. Whether GRK2 mediated-EP4 over-desensitization reduces the level of cAMP and inhibits M2 polarization in RA is unclear. Here we observed M1 macrophages were dominant in peritoneal macrophages (PMs), bone-marrow-derived macrophages (BMMs) and synovial macrophages of collagen-induced arthritis (CIA) mice. PGE2 stimulated M2 polarization via the EP4-cAMP-CREB in normal mice, while failed to promote M2 polarization in the PMs of CIA mice. Further, we found the EP4 over-desensitization stimulated by PGE2 induced abnormal PGE2-cAMP-CREB signaling as well as the imbalance of macrophage polarization. Targeted disruption of GRK2 in Raw264.7 (RAW) through GRK2 #siRNA or CRISPR/Cas9 downregulated the M1 macrophage markers, upregulated the M2 macrophage markers and the EP4 membrane localization. The reduced M1/M2 ratio and increased p-CREB expression were observed in BMMs and PMs of GRK2+/− mice. This study highlighted a novel role of GRK2 in regulating macrophages function in RA and provided new idea for precision treatment of RA. http://bit.ly/354vT0S

[thenicerstuff]

Day 60/365 Wearing many hats... my abNOMO life. First day of March #kittytales2019 #vocalcoachestella #estellaonkeys #singingestella #vpestella #photographerestella https://www.instagram.com/p/BufeWW-gRK2/?utm_source=ig_tumblr_share&igshid=rylm4nkhn95x

[awesomearabmedicalpro]

أخبار AHA: العلماء يجدون صلة بيولوجية بين ارتفاع ضغط الدم وسرطان الثدي

الفئة: أمراض القلب | الأورام | أخبار

العودة إلى أخبار الصحة

آخر تحديث: 06 سبتمبر 2019.

التعليقات: (0)

اخبر صديق

الجمعة ، 6 سبتمبر ، 2019 (أخبار جمعية القلب الأمريكية) – حدد الباحثون بروتينًا قد يكون عامل خطر لارتفاع ضغط الدم وسرطان الثدي.

و��دت دراسات سابقة أن النساء المصابات بارتفاع ضغط الدم لديهن مخاطر أعلى بنسبة 15٪ من الإصابة بسرطان الثدي مقارنة بالنساء المصابات بضغط دم طبيعي. تبين أن ارتفاع مستويات البروتين GRK4 (مستقبلات G- البروتين كيناز 4) يسبب ارتفاع ضغط الدم ، ويسمى أيضًا ارتفاع ضغط الدم. أظهرت الدراسة الجديدة ، التي تم تقديمها يوم الجمعة في جلسات علمية ارتفاع ضغط الدم للجمعية الأمريكية للقلب في نيو أورليانز ، أن بروتين GRK4 موجود في خلايا سرطان الثدي ولكن ليس في خلايا الثدي الطبيعية.

وقال الدكتور وي يوي ، الباحث الرئيسي في الدراسة وعالم الأبحاث في كلية طب جامع�� فرجينيا في شارلوتسفيل: "السرطان وارتفاع ضغط الدم يشتركان في عوامل الخطر الشائعة". "لقد وجد بحثنا السابق في مختبرنا على GRK4 أنه ينظم بواسطة جينة تسمى c-Myc ، والتي تلعب دورًا في العديد من أنواع السرطان ، بما في ذلك سرطان الثدي. وقد أدى ذلك بنا إلى افتراض أن GRK4 يمكن أن تكون حلقة وصل."

ما يقرب من نصف جميع البالغين المصابين بارتفاع ضغط الدم هم من النساء. بعد سن 65 ، تكون النساء أكثر عرضة من الرجال لارتفاع ضغط الدم. يمكن للحمل وأدوية تحديد النسل وانقطاع الطمث زيادة خطر الإصابة بارتفاع ضغط الدم. إذا تركت دون علاج ، يمكن أن يسبب مشاكل صحية مثل أمراض القلب والسكتة الدماغية وفقدان البصر.

في النساء ، يعد سرطان الثدي أكثر أنواع السرطان شيوعًا وهو السبب الرئيسي الثاني للوفاة بالسرطان.

وقالت الدكتورة فيسنا دي جاروفيتش ، رئيسة قسم أمراض الكلى وارتفاع ضغط الدم: "بينما أظهرت الدراسات السابقة أن خطر الإصابة بسرطان الثدي يزداد لدى النساء المصابات بارتفاع ضغط الدم ، فإن هذه الدراسة تضيف إلى المعرفة الحالية من خلال توفير الآليات الجزيئية التي تقوم عليها هذه الرابطة". البحث في مايو كلينك في روتشستر ، مينيسوتا.

وقال جاروفيتش ، الذي لم يشارك في البحث الجديد ، إن دراسات مثل هذه الدراسة التي تحدد الآليات الجزيئية ومسارات الإشارة التي تسبب المرض يمكن أن تقدم رؤى جديدة لخيارات العلاج.

ليست كل أورام الثدي هي نفسها. بحثت الدراسة عن GRK4 في نوعين محددين من سرطان الثدي ، والمعروف باسم الهرمونات الحساسة والسلبية الثلاثية.

وقال يوي: "قد لا يكون استنتاجنا قابلاً للتطبيق على أنواع أخرى من سرطان الثدي".

لاحظ غاروفيتش أن الاختلافات الوراثية GRK4 قد لا تكون هي نفسها في جميع المجموعات العرقية. وقالت إن الدراسات التي تبحث عن GRK4 لدى النساء المصابات بسرطان الثدي عبر المجموعات العرقية والإثنية ، قد توفر نظرة ثاقبة للاختلافات القائمة سابقًا على العرق في نوع الورم ، واستجابة العلاج والنتائج.

GRK4 هو واحد من سبعة بروتينات GRK. بحثت دراسات أخرى عن GRK2 و GRK5 في أنواع مختلفة من السرطانات ، لكن Yue قالت إن مجموعتهم هي الأولى التي تبحث عن صلة بين GRK4 وارتفاع ضغط الدم وسرطان الثدي. وقالت "لا أحد يعمل على هذا."

قال يوي إن هذا الجزيء فريد لأنه لا يتم التعبير عنه عادة – أي أنه يصنع جينًا في البروتين في أنسجة الثدي ، مما يجعله هدفًا محتملًا لتطوير الدواء.

"الدواء الذي يستهدف GRK4 يمكن أن يستخدم لعلاج المرضى الذين يعانون من ارتفاع ضغط الدم وسرطان الثدي."

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[batsort93-blog]

The heart 'talks' to fat cells

Like sending a letter through the mail or a text over a cellular network, the heart can generate messages that travel long distances through the body. Those messages ultimately reach fat cells, new research by scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) shows.

"The ability of the heart to communicate directly with fat had been suspected, but our study is the first to provide evidence of crosstalk between heart and fat tissue that is regulated by the enzyme, G protein-coupled receptor kinase 2 (GRK2)," said senior investigator Walter J. Koch, PhD, W.W. Smith Endowed Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology, and Director of the Center for Translational Medicine at LKSOM.

The findings could have implications for modulating weight gain in patients with heart failure, a condition that arises when the heart can no longer effectively pump blood through the body.

In the breakthrough paper, published online May 16 in the journal JCI Insight, Dr. Koch and colleagues show that the heart relies on a cardiac-specific messenger, the signaling enzyme, GRK2, to relay information about metabolism to fat cells.

"GRK2 signaling in the heart effectively regulates fat accumulation in the body," said Dr. Koch. "Through this pathway, the heart 'talks' to fat and alters how fat responds to certain conditions." In previous work, Dr. Koch's laboratory showed that GRK2 serves essential roles in both normal heart function and heart failure.

The researchers carried out their investigation in mice with GRK2 activity inhibited in the heart. When fed a high fat diet, GRK2-inhibited mice accumulated significantly more fat than their littermates with normal GRK2 expression. The experiment was repeated in mice with GRK2 overexpressed in the heart, mimicking the increase in GRK2 that occurs in heart failure in humans. When given a high fat diet, these mice gained less body weight compared to their normal littermates.

Using complex metabolomics, a way of investigating metabolites associated with cellular processes, Dr. Koch's team found that GRK2 signaling specifically altered branched chain amino acid (BCAA) and endocannabinoid metabolism in the heart. GRK2-overexpressing mice on high fat diets had metabolite profiles that were distinct from those of GRK2-inhibited mice and normal animals.

"We also took the work a step further and identified one BCAA metabolite that enhanced fat cell differentiation in vitro," Dr. Koch said. His team plans next to look for other metabolites and protein factors that are involved in crosstalk between the heart and fat tissue.

Story Source:

Materials provided by Temple University Health System. Note: Content may be edited for style and length.

Source: https://www.sciencedaily.com/releases/2019/05/190509115437.htm

[1hourtranscripts]

Mechanistic insights into how valsartan may aid in attenuating pathogenesis-associated with Myocardial infarction: Valsartan(brand name: Diovan),  used in the treatment of high blood pressure and congestive heart failure, decreases IRF3 (Interferon regulatory transcription factor-3), GM-CSF (Granulocyte-macrophage colony-stimulating factor) and GRK2(G protein-coupled receptor kinase) expression, inhibits undue leucocyte activation and invasion, suppresses recruitment of inflammatory cells, inhibits ventricular dilation, and promotes heart repair and survival, via up-regulation of its target gene, 25/October/2018, 2.27 pm – Genome Discovery https://cstu.io/da514c

[aginginbeauty]

GRK2 as a Target for the Treatment of Heart Fibrosis

GRK2 as a Target for the Treatment of Heart Fibrosis

Fibrosis is one of the characteristics of old tissue, a disarraying of the normal processes of regeneration and tissue maintenance that leads to the formation of scar-like structures and consequent loss of tissue function. This is especially notable in the heart, in the kidneys, and in some lung conditions. Little progress was made towards effective therapies until it was determined that senesce…

[rebuilderremodeling]

@Messanger_Molec: Cardiac Fibroblast GRK2 Deletion Enhances Contractility and Remodeling Following Ischemia/Reperfusion Injury.… https://t.co/mHPBtoKAeH

http://twitter.com/Messanger_Molec

[calangonapistarcdrift]

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[cancersfakianakis1]

The influence of TNF-α and Ang II on the proliferation, migration and invasion of HepG2 cells by regulating the expression of GRK2

Abstract

Purpose

Hepatocellular carcinoma (HCC) is a common digestive system malignancy that is associated with a poor prognosis. This study researched the interaction of tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II) in HCC cells proliferation, migration and invasion and examined their influence on the expression of G protein-coupled receptor kinase 2 (GRK2) and relevant receptors.

Methods

Cell Counting Kit-8 and Transwell assays were performed to evaluate the effects of TNF-α and Ang II on HepG2 cells proliferation, migration and invasion. Flow cytometry was used to investigate the expression of tumor necrosis factor receptor 1 (TNFR1), angiotensin II type 1 (AT1R) and type 2 receptors (AT2R) on the surface of HepG2 cells. Additionally, Western blot was performed to assess the modulation of GRK2 expression by TNF-α and Ang II in HepG2 cells. Meanwhile, GRK2 siRNA-transfected HepG2 cells were used to confirm the effects of GRK2, TNF-α and Ang II on the proliferation, migration and invasion of GRK2-knockdown HCC cells. Finally, the expression of TNF-α, Ang II, TNFR1, AT1R, AT2R and GRK2 proteins in HCC, tumor-adjacent and normal liver tissues were tested by immunohistochemistry.

Results

The data demonstrated that TNF-α and Ang II can enhance the proliferation, migration and invasion of HepG2 cells through suppressing GRK2 expression but that the two reagents combined did not have synergistic effects. Moreover,overexpression of TNFR1 and AT1R perhaps promoted the formation and progression of HCC, while high AT2R expression had the opposite effect.

Conclusions

This study provides new ideas for the prevention and treatment of HCC by researching the interaction and probable mechanism of different bioactive factors associated with HCC.

http://ift.tt/2mH5K1K

[rnomics]

Long noncoding #RNA UCA1 promotes tumour metastasis by inducing GRK2 degradation in gastric #cancer.

Related Articles Long noncoding #RNA UCA1 promotes tumour metastasis by inducing GRK2 degradation in gastric #cancer. #cancer Lett. 2017 Nov 01;408:10-21 Authors: Wang ZQ, He CY, Hu L, Shi HP, Li JF, Gu QL, Su LP, Liu BY, Li C, Zhu Z Abstract Increasing evidence demonstrates that long noncoding #RNAs (l#ncRNAs) regulate gene and protein expression by exerting an influence on transcriptional and post-transcriptional processes. Here, we report that the l#ncRNA UCA1 increases the metastatic ability of gastric #cancer (GC) cells by regulating GRK2 protein stability by promoting Cbl-c-mediated GRK2 ubiquitination and degradation. This process then activates the ERK-MMP9 signalling pathway. Furthermore, we demonstrate that GRK2 is downregulated in GC cells and that silencing of GRK2 might cause similar phenotypic changes and signalling pathway activation as those induced by elevated UCA1 in GC cells. Our results suggest that UCA1 might function as a mediator of protein ubiquitination and may be a promising molecular target for GC therapy. PMID: 28843497 [PubMed - indexed for MEDLINE] http://bit.ly/2hx9TEO #Pubmed

[rcmart]

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[neurosciencenews]

Protein GRK2 Appears to Help Regulate Body Clock

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body’s internal clock and points the way to remedies for jet lag and shift work exhaustion.

The research is in Cell Reports. (full open access)

Research: "GRK2 Fine-Tunes Circadian Clock Speed and Entrainment via Transcriptional and Post-translational Control of PERIOD Proteins" by Neel Mehta, Arthur H. Cheng, Cheng-Kang Chiang, Lucia Mendoza-Viveros, Harrod H. Ling, Abhilasha Patel, Bo Xu, Daniel Figeys, and Hai-Ying M. Cheng in Cell Reports doi:10.1016/j.celrep.2015.07.037

Image: In this study, the researchers determined that GRK2 was also abundantly expressed in the SCN throughout all phases of the circadian cycle. Credit: University of Toronto Mississauga.

[drift4fun]

A minha experiência com carrinhos de controle remoto de drift - parte 3 de 3

Essa é uma continuação do artigo: http://drift4fun.tumblr.com/post/116382320798/a-minha-experiencia-com-carrinhos-de-controle

Ja estava nos meus planos ter um segundo chassi, e como vendi o Sakura XI Sport era hora de compra-lo, inicialmente a idéia era pegar um segundo MST XXX-D em sua versão PRO (de plástico) mas depois da experiência relatada no artigo anterior optei por adquirir um GRK2+ 

Análise do GRK2+

Assim como o XXX-D Vip da MST o GRK2+ fabricado pela R31 House também vem com carbono e peças em alumínio, é igualmente bonito, o chassi em si é mais pesado e robusto, o XXX-D Vip é mais flexível.

Esse chassi na época custou cerca de R$ 2.300 (isso mesmo), foi adquirido através do Seiji da SlowFreaks team, que foi super rápido no atendimento, montagem e envio do chassi, recomendo.

Pontos positivos do GRK2+

É um chassi bem robusto, bem sólido e consistente, o meu veio com CS de 1.6 e adicionei a mesma eletrônica do XXX-D Vip (Combo Speed Passion Dokyo DriftSpec 10.5T Sensored + servo Savox 1251 low profile) 

No asfalto deixou um pouco a desejar (não significa que anda ruim no asfalto, mas eu particularmente não consegui chegar em um setup legal), sempre muito arisco e de difícil controle, mas, em contra partida, deu show no carpete, com uma estabilidade incrível, em pouco tempo e com poucos ajustes o rc tava na mão pra andar no carpete.

Pontos negativos do GRK2+

Veio com defeito. Pois é, infelizmente o lote que compramos (na época foram compradas 3 unidades da nossa equipe e mais uma de um amigo nosso) todos acabaram apresentando, mais cedo ou mais tarde, defeito no Oneway :(

GRK2+ Oneway:

Foi um pouco frustrante, confesso, mas o Seiji prestou uma ótima assistência e a R31 House nos enviou a peça que veio com problema.

Após alguns meses tive outro problema, um dos shafts dianteiros empenou, um amigo ja havia relatado o mesmo caso com o GRK2+ dele e falou que achava esse um ponto fraco do chassi, felizmente consegui comprar a peça aqui mesmo no Brasil e não voltou a dar esse problema até agora.

GRK2+ Swing shaft:

Parafusos:

São péssimos, acho que é o maior ponto fraco desse chassi, não entendo porque utilizaram parafusos tão ruins, não adianta vir com a conversa que não utilizei a chave certa, pois utilizo o kit de chaves próprio para isso e toda a semana mexo no MST (por causa do desgaste bem maior no asfalto) e NUNCA remoeu um parafuso sequer, no GRK a segunda vez que fui dar manutenção remoeu uns quatro ou cinco de uma vez só!

Minha opinião sobre o chassi GRK2+

No geral é um carro muito bom, faz um drift suave e tirando esse problema com o Oneway e o shaft empenado, a impressão que tenho é que ele é mais resistente.

Tem um ótimo sistema de direção, bem pensado e MUITO melhor do que o sistema que o do XXX-D Vip, porém não alcança um bom esterço como o rival da MST por não vir com bandejas em Y.

De 0 a 10 eu daria um 7, esse chassi poderia ter as facilidades de montagem do XXX, como por exemplo a peça onde fica presa o motor, no XXX é extremamente simples, ela corre sobre um trilho que facilita MUITO a instalação e manutenção, o ajuste do Toe também é bem mais prático no MST dentre outros pequenos detalhes.