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Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats
Conclusion Principal findings of this work are that abnormal Ca2+ transient amplitude, contractile dysfunction; and impaired relaxation of MetS cardiomyocytes underlies intrinsic dysfunctional RyR2 and SERCA pump. Abnormal activity of RyRs was evidenced by its decreased ability to bind [3H]-ryanodine. Although the MetS condition does not modify RyR2 protein expression, its phosphorylation at Ser2814 is decreased, which impairs its capacity for activation during ECC. The dysfunctional RyRs, together with a decreased activity of SERCA pump due to decreased Thr17-PLN phosphorylation suggest a downregulation of CaMKII in MetS...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Atrial Transcriptional Profiles of Molecular Targets Mediating Electrophysiological Function in Aging and Pgc-1 β Deficient Murine Hearts
Conclusion: These findings limit the possible roles of gene transcriptional changes in previously reported age-dependent pro-arrhythmic electrophysiologial changes observed in Pgc-1β-/- atria to an altered Ca2+-ATPase (Atp2a2) expression. This directly parallels previously reported arrhythmic mechanism associated with p21-activated kinase type 1 deficiency. This could add to contributions from the direct physiological outcomes of mitochondrial dysfunction, whether through reactive oxygen species (ROS) production or altered Ca2+ homeostasis. Introduction Atrial arrhythmias constitute a major public health pro...
Source: Frontiers in Physiology - April 23, 2019 Category: Physiology Source Type: research

Shengui Sansheng San Ameliorates Cerebral Energy Deficiency via Citrate Cycle After Ischemic Stroke
Conclusion In summary, SSS extraction significantly ameliorates cerebral energy metabolism via boosting citrate cycle, which mainly embodies the enhancements of blood glucose concentration, glucose and lactate transportation and glucose utilization, as well as the regulations of relative enzymes activities in citrate cycle. These ameliorations ultimately resulted in numerous ATP yield after stroke, which improved neurological function and infarcted volume. Collectively, it suggests that SSS extraction has exerted advantageous effect in the treatment of cerebral ischemia. Ethics Statement All animal operations were accor...
Source: Frontiers in Pharmacology - April 22, 2019 Category: Drugs & Pharmacology Source Type: research

Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer ’s Disease Through Activation of BDNF-TrkB Signaling Pathway
Conclusion The data in this manuscript demonstrates that apelin-13 upregulates BDNF against STZ-induced congnitive impairment by suppressing glial cell activity and inflammatory factors release. This suggests apelin signaling may be a new target in the treatment of AD. Ethics Statement All experimental protocols were carried out according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals approved by the Central South University at XiangYa Animal Care and Use Committee. Author Contributions XqQ and LH conceived the study and contributed to its experimental design. HqL carried out the...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Role of TREK-1 in Health and Disease, Focus on the Central Nervous System
Conclusion and Perspectives Since their cloning 20 years ago, the physiological importance of TREK-1 channels has continued to grow (Figure 3). Today, TREK-1 channels have been shown to be important and their presence is essential in a number of physiopathological processes. Their involvement in these different processes demonstrate the necessity to design pharmacological modulators, activators or inhibitors, of these channels to correct any TREK-1-related dysfunctions. Despites a number of studies and many molecule screenings, only few putative new drugs were identified. The activators belonging to the ML and BL series ...
Source: Frontiers in Pharmacology - April 10, 2019 Category: Drugs & Pharmacology Source Type: research