Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation

Increased abundance of GRK2 [G protein–coupled receptor (GPCR) kinase 2] is associated with poor cardiac function in heart failure patients. In animal models, GRK2 contributes to the pathogenesis of heart failure after ischemia-reperfusion (IR) injury. In addition to its role in down-regulating activated GPCRs, GRK2 also localizes to mitochondria both basally and post-IR injury, where it regulates cellular metabolism. We previously showed that phosphorylation of GRK2 at Ser670 is essential for the translocation of GRK2 to the mitochondria of cardiomyocytes post-IR injury in vitro and that this localization promotes cell death. Here, we showed that mice with a S670A knock-in mutation in endogenous GRK2 showed reduced cardiomyocyte death and better cardiac function post-IR injury. Cultured GRK2-S670A knock-in cardiomyocytes subjected to IR in vitro showed enhanced glucose-mediated mitochondrial respiratory function that was partially due to maintenance of pyruvate dehydrogenase activity and improved glucose oxidation. Thus, we propose that mitochondrial GRK2 plays a detrimental role in cardiac glucose oxidation post-injury.
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news

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Authors: Jin B, Ji F, Zuo A, Liu H, Qi L, He Y, Wang Q, Zhao P Abstract Heart failure (HF) is a disease with high morbidity and mortality. In patients with HF, decreased cardiac output and blood redistribution results in decreased intestinal perfusion and destruction of intestinal barrier. Microorganisms and endotoxins can migrate into the blood circulation, aggravating systemic inflammation and HF. Trimethylamine N-oxide (TMAO) is highly closed to the occurrence of HF. However, the exact mechanism between TMAO and HF remains unclear.To investigate the role of TMAO in transverse-tubule (T-tubule) in the cultured ca...
Source: International Heart Journal - Category: Cardiology Tags: Int Heart J Source Type: research
Conclusions: Our studies show that Celastrol inhibits Ang II-induced cardiac dysfunction by inhibiting STAT3 activity. PMID: 32098592 [PubMed - as supplied by publisher]
Source: Circulation Research - Category: Cardiology Authors: Tags: Circ Res Source Type: research
In conclusion, taller body height at the entry to adulthood, supposed to be a marker of early-life environment, is associated with lower risk of dementia diagnosis later in life. The association persisted when adjusted for educational level and intelligence test scores in young adulthood, suggesting that height is not just acting as an indicator of cognitive reserve. A Comparison of Biological Age Measurement Approaches https://www.fightaging.org/archives/2020/02/a-comparison-of-biological-age-measurement-approaches/ Researchers here assess the performance of a range of approaches to measuring biological...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Despite the development of new drugs and therapeutic strategies, mortality and morbidity related to heart failure (HF) remains high. It is also the leading cause of global mortality. Several concepts have been proposed to explore the underlying pathogenesis of HF, but there is still a strong need for more specific and complementary therapeutic options. In recent years, accumulating evidence has demonstrated that changes in the composition of gut microbiota, referred to as dysbiosis, might play a pivotal role in the development of several diseases, including HF. HF-associated decreased cardiac output, resu...
Source: ENDOCR REV - Category: Endocrinology Authors: Tags: Rev Endocr Metab Disord Source Type: research
AbstractDespite the development of new drugs and therapeutic strategies, mortality and morbidity related to heart failure (HF) remains high. It is also the leading cause of global mortality. Several concepts have been proposed to explore the underlying pathogenesis of HF, but there is still a strong need for more specific and complementary therapeutic options. In recent years, accumulating evidence has demonstrated that changes in the composition of gut microbiota, referred to as dysbiosis, might play a pivotal role in the development of several diseases, including HF. HF-associated decreased cardiac output, resulting in b...
Source: Reviews in Endocrine and Metabolic Disorders - Category: Endocrinology Source Type: research
In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ConclusionsWe provide the first evidence for a clinically significant BSI caused byP. copri and its relationship to aPrevotella-rich gut microbiota in the HF patient setting. When strengthening the pathogenicity ofP. copri, the present case suggests that the gut may be a source of BSI caused by the rare anaerobic organism. Future studies are necessary to assess the role of the gut microbiota profiling for precise identification and targeted treatment of patients at high risk of BSI.
Source: Gut Pathogens - Category: Microbiology Source Type: research
Publication date: Available online 13 September 2019Source: Life SciencesAuthor(s): Emiliana Echeverría, Ana Julia Velez Rueda, Maia Cabrera, Ezequiel Juritz, Valeria Burghi, Lucas Fabián, Carlos Davio, Pablo Lorenzano Menna, Natalia Cristina FernándezAbstractAimsG protein-coupled receptor (GPCR) kinases (GRKs) are mainly involved in the desensitization of GPCRs. Among them, GRK2 has been described to be upregulated in many pathological conditions and its crucial role in cardiac hypertrophy, hypertension, and heart failure promoted the search for pharmacological inhibitors of its activity. There have b...
Source: Life Sciences - Category: Biology Source Type: research
Conclusion: Carvacrol protected against DCM in mice with T1DM and T2DM by restoring PI3K/AKT signaling-mediated GLUT4 membrane translocation and is a potential treatment of DCM.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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