Journal of Bioenergetics and Biomembranes最新文献

Diabetes mellitus (DM) is a chronic syndrome involving neuropathic pain. Increased oxidative stress in DM is assumed to increase free reactive oxygen radicals (ROS) and causes diabetic damage. The sciatic nerve (ScN) and dorsal root ganglion (DRG) both contain high levels of the TRPV1 channel, which is triggered by capsaicin and ROSs and results in increased Ca²⁺ entry into the neurons. Alpha-lipoic acid (ALA) is considered an important part of the antioxidant system. To better characterize the protective effects of ALA on the DM-induced neuronal through TRPV1 modulation, we investigated the role of ALA on DM-induced neuropathic pain, oxidative ScN, and DRG damage in diabetic rats. Forty adult Wistar albino female rats were divided into four groups as control, ALA (50 mg/kg for 14 days), streptozotocin (STZ and 45 mg/kg and single dose), and STZ + ALA. Rats were used for the pain tests. After obtaining the DRGs and ScN, they were used for plate reader, patch-clamp, and laser confocal microscope analyses. We observed the modulator role of ALA on the thresholds of mechanical withdrawal pain (von Frey test) and hot sensitivity pain (hot plate test) in the STZ + ALA group. The treatment of ALA decreased STZ-induced increase of TRPV1 current densities, intracellular free Ca²⁺ concentrations (Fura-2 and Fluo - 3/AM), ROS, caspase 3, caspase 9, mitochondrial membrane potential, and apoptosis values in the ScN and DRG neurons, although its treatment induced the increase of cell viability and body weight gain. The treatment of ALA acted a neuroprotective role on the TRPV1 channel stimulation-mediated Ca²⁺ influx, neuropathic pain, and neuronal damage in diabetic rats. The neuroprotective role of ALA treatment can be explained by its modulating the TRPV1 channel activity, intracellular Ca²⁺ increase-induced oxidative stress, and apoptosis.

The individual study of [Formula: see text] and [Formula: see text] dynamics respectively in a [Formula: see text]-cell has yielded limited information about the cell functions. But the systems biology approaches for such studies have received very little attention by the research workers in the past. In the present work, a system-dynamics model for the interdependent [Formula: see text] and [Formula: see text] signaling that controls insulin secretion in a [Formula: see text]-cell has been suggested. A two-way feedback system of [Formula: see text] and [Formula: see text] has been considered and one-way feedback between [Formula: see text] and insulin has been implemented in the model. The finite element method along with the Crank-Nicolson method have been applied for simulation. Numerical results have been used to analyze the impact of perturbations in [Formula: see text] and [Formula: see text] dynamics on insulin secretion for normal and Type-2 diabetic conditions. The results reveal that Type-2 diabetes comes from abnormalities in insulin secretion caused by the perturbation in buffers and pumps (SERCA and PMCA).

Vascular calcification (VC) and ischemia reperfusion (IR) injury is characterised to have mitochondrial dysfunction. However, the impact of dysfunctional mitochondria associated with vascular calcified rat kidney challenged to IR is not explored and is addressed in the present study. Male Wistar rats were treated with adenine for 20 days to induce chronic kidney dysfunction and VC. After 63 days, renal IR protocol was performed with subsequent recovery for 24 h and 7 days. Various mitochondrial parameters and biochemical assays were performed to assess kidney function, IR injury and its recovery. Adenine-induced rats with VC, decreased creatinine clearance (CrCl), and severe tissue injury demonstrated an increase in renal tissue damage and decreased CrCl after 24 h of IR (CrCl in ml: IR-0.220.02, VC-IR-0.050.01). Incidentally, the 24 h IR pathology in kidney was similar in both VC-IR and normal rat IR. But, the magnitude of dysfunction was higher with VC-IR due to pre-existing basal tissue alterations. We found severed deterioration in mitochondrial quantity and quality supported by low bioenergetic function in both VC basal tissue and IR challenged sample. However, post 7 days of IR, unlike normal rat IR, VC rat IR did not improve CrCl and corresponding mitochondrial damage in terms of quantity and its function were observed. Based on the above findings, we conclude that IR in VC rat adversely affect the post-surgical recovery, mainly due to the ineffective renal mitochondrial functional restoration from the surgery.

Pentaamino acid fullerene C₆₀ derivative is a promising nanomaterial, which exhibited antihyperglycemic activity in high-fat diet and streptozotocin-induced diabetic rats. This study investigates the effect of pentaaminoacid C₆₀ derivative (PFD) in rats with metabolic disorders. Rats were assigned to 3 groups (of 10 rats each) as follows: Group 1 (normal control), group 2 included the protamine-sulfate-treated rats (the untreated group of animals with the model metabolic disorder); group 3 (Protamine sulfate + PFD) included the protamine-sulfate-treated model rats that received an intraperitoneal injection of PFD. Metabolic disorder in rats was initiated by protamine sulfate (PS) administration. The PS + PFD group was injected intraperitoneally with PFD solution (3 mg/kg). Protamine sulfate induces biochemical changes (hyperglycemia, hypercholesterolemia, and hypertriglyceridemia) in the blood and morphological lesions in rat liver and pancreas. The potassium salt of fullerenylpenta-N-dihydroxytyrosine in protamine sulfate-induced rats normalized blood glucose level and the serum lipid profile and improved hepatic function markers. Treatment with PFD restored pancreas islets and liver structure of protamine sulfate-induced rats compared to the untreated group. PFD is a promising compound for further study as a drug against metabolic disorders.

Endothelial dysfunction is a key early link in the pathogenesis of atherosclerosis, and the accumulation of senescent vascular endothelial cells causes endothelial dysfunction. Phosphoenolpyruvate (PEP), which is a high-energy glycolytic intermediate, protects against ischemia-reperfusion injury in isolated rat lung, heart, and liver tissue by quickly providing ATP. However, it was reported that serum PEP concentrations are 13-fold higher in healthy elderly compare to the young. Unlike that of other cell types, the energy required for the physiological function of endothelial cells is mainly derived from glycolysis. Recently, it is unclear whether circulating accumulation of PEP affects endothelial cell function. In this study, we found for the first time that 50-250 μM of PEP significantly promoted THP-1 monocyte adhesion to human umbilical vein endothelial cells (HUVECs) through increased expression of vascular endothelial adhesion factor 1 (VCAM1) and intercellular adhesion factor 1 (ICAM1) in HUVECs. Meanwhile, 50-250 μM of PEP decreased the expression of endothelial nitric oxide synthase (eNOS) and cellular level of nitric oxide (NO) in HUVECs. Moreover, PEP increased levels of ROS, enhanced the numbers of SA-β-Gal-positive cells and upregulated the expression of cell cycle inhibitors such as p21, p16 and the phosphorylation level of p53 on Ser15, and the expression of proinflammatory factors including TNF-α, IL-1β, IL-6, IL-8, IL-18 and MCP-1 in HUVECs. Furthermore, PEP increased both oxygen consumption rate (OCR) and glycolysis rate, and was accompanied by reduced NAD⁺/NADH ratios and enhanced phosphorylation levels of AMPKα (Thr172), p38 MAPK (T180/Y182) and NF-κB p65 (Ser536) in HUVECs. Notably, PEP had no significant effect on hepG2 cells. In conclusion, these results demonstrated that PEP induced dysfunction and senescence in vascular endothelial cells through stimulation of metabolic reprogramming.

Animals suffer hypoxia when their oxygen consumption is larger than the oxygen available. Hypoxia affects the white shrimp Penaeus (Litopenaeus) vannamei, both in their natural habitat and in cultivation farms. Shrimp regulates some enzymes that participate in energy production pathways as a strategy to survive during hypoxia. Glucose-6-phosphatase (G6Pase) is key to maintain blood glucose homeostasis through gluconeogenesis and glycogenolysis. We previously reported a shrimp G6Pase gene (G6Pase1) and in this work, we report a second isoform that we named G6Pase2. The expression of the two isoforms was evaluated in oxygen limited conditions and during silencing of the transcription factor HIF-1. High G6Pase activity was detected in hepatopancreas followed by muscle and gills under good oxygen and feeding conditions. Gene expression of both isoforms was analyzed in normoxia, hypoxia and reoxygenation in hepatopancreas and gills, and in HIF-1-silenced shrimp. In fed shrimp with normal dissolved oxygen (DO) (5.0 mg L^- 1 DO) the expression of G6Pase1 was detected in gills, but not in hepatopancreas or muscle, while G6Pase2 expression was undetectable in all three tissues. In hepatopancreas, G6Pase1 is induced at 3 and 48 h of hypoxia, while G6Pase2 is down-regulated in the same time points but in reoxygenation, both due to the knock-down of HIF-1. In gills, only G6Pase1 was detected, and was induced by the silencing of HIF-1 only after 3 h of reoxygenation. Therefore, the expression of the two isoforms appears to be regulated by HIF-1 at transcriptional level in response to oxygen deprivation and subsequent recovery of oxygen levels.

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia that affects practically all tissues and organs, being the brain one of most susceptible, due to overproduction of reactive oxygen species induced by diabetes. Eryngium carlinae is a plant used in traditional Mexican medicine to treat diabetes, which has already been experimentally shown have hypoglycemic, antioxidant and hypolipidemic properties. The green synthesis of nanoparticles is a technique that combines plant extracts with metallic nanoparticles, so that the nanoparticles reduce the absorption and distribution time of drugs or compounds, increasing their effectiveness. In this work, the antioxidant effects and mitochondrial function in the brain were evaluated, as well as the hypoglycemic and hypolipidemic effect in serum of both the aqueous extract of the aerial part of E. carlinae, as well as its combination with silver nanoparticles of green synthesis. Administration with both, extract and the combination significantly decreased the production of reactive oxygen species, lipid peroxidation, and restored the activity of superoxide dismutase 2, glutathione peroxidase, and electron transport chain complexes in brain, while that the extract-nanoparticle combination decreased blood glucose and triglyceride levels. The results obtained suggest that both treatments have oxidative activity and restore mitochondrial function in the brain of diabetic rats.

In this study, we intend to explore the potential function of l-ascorbic acid in hypoxia-reoxygenation (H/R)-induced damage of CMECs and its related molecular mechanism. With different concentrations of l-ascorbic acid treatment, the proliferation, migration, inflammation and autophagy of cardiac microvascular endothelial cells (CMECs) were determined by several biological experiments. Si-HMGB1 transfection was used to reduce HMGB1 expression and to detect the function of HMGB1 in H/R-induced damage of CMECs. Under H/R condition, the proliferation and migration abilities of CMECs were reduced, and the inflammation and autophagy of CMECs were increased. Whereas, after l-ascorbic acid treatment, the reduction in the proliferation and migration of CMECs, as well as the increase in the inflammation and autophagy of CMECs induced by H/R were reversely altered. HMGB1 was confirmed as a specific target of l-ascorbic acid, and si-HMGB1 treatment strengthened the beneficial effect of l-ascorbic acid on H/R-induced damage of CMECs, followed by further reduction in the proliferation and migration abilities of CMECs, as well as the increase in the inflammation and autophagy of CMECs. Few studies have reported the function of l-ascorbic acid in myocardial ischemia on CMECs, but our experimental data showed that l-ascorbic acid treatment could ameliorate the H/R-induced damage of CMECs by regulating HMGB1 expression.

Aim/introduction: Diabetes Mellitus is a chronic degenerative disease, and its main biochemical characteristic is hyperglycemia due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Hyperglycemia causes dyslipidemia and stimulates oxidative damage, leading to the main symptoms, such as fatigue and culminates in diabetic complications. Previous studies have shown that ATP-sensitive potassium channels counteract muscle fatigue and metabolic stress in healthy mouse models. To determine the effect of diazoxide on muscle strength development during diabetes, we tested the effect of diazoxide in streptozotocin-diabetic rats in muscle function, lipid profile and oxidative stress biomarkers.

Materials and methods: Wistar rats were divided into 4 groups of six animals each: (1) Control group, (2) diabetes group, (3) Control group + diazoxide, and (4) Diabetic + diazoxide (DB + DZX). 4 weeks after rats were sacrificed, soleus and extensor digitorum longus muscles (EDL) were extracted to prepare homogenates and serum was obtained for biochemical measurements. Oxidative damage was evaluated by the thiobarbituric acid method and the fluorescent for reactive oxygen species (ROS) probe 2,4-H₂DCFDA, respectively.

Results: Diabetic rats with diazoxide administration showed an increase in the development of muscle strength in both muscles; in turn, the onset of fatigue was longer compared to the group of diabetic rats without treatment. Regarding the lipid profile, diazoxide decreased total cholesterol levels in the group of diabetic rats treated with diazoxide (x̅46.2 mg/dL) compared to the untreated diabetic group (x̅=104.4 mg/dL); secondly, diazoxide decreased triglyceride concentrations (x̅=105.3 mg/dL) compared to the untreated diabetic rats (x̅=412.2 mg/dL) as well as the levels of very low-density lipoproteins (x̅=20.4 mg/dL vs. x̅=82.44 mg/dL). Regarding the various markers of oxidative stress, the diabetic group treated with diazoxide was able to reduce the concentrations of TBARS and total reactive oxygen species as well as preserve the concentrations of reduced glutathione.

Conclusion: Diazoxide administration in diabetic rats increases muscle strength development in EDL and soleus muscle, decreases fatigue, reduces cholesterol and triglyceride concentrations and improves oxidative stress parameters such as TBARS, ROS, and glutathione status.

Objective: Data in the GEO database (GSE63067) showed that G protein-coupled receptor 39 (GPR39) was down-regulated in tissues from patients with non-alcoholic fatty liver disease (NAFLD). It was intended to explore the mechanism of GPR39 in NAFLD.

Methods: HepG2 cells were treated with a mixture of oleic acid and palmitic acid (OA/PA) to mimic NAFLD cell models. The level of GPR39 and the functions of GPR39 on cellular oxidative stress, lipid accumulation, the SIRT1/Nrf2 signaling and mitochondrial dysfunction were assessed. To verify the mediation of the SIRT1 signaling pathway in GPR39 regulation, cells were subjected to SIRT1 inhibitor EX-527 treatment. Afterwards, the abovementioned aspects of cells were all determined.

Results: GPR39 presented a downward trend in response to OA/PA. GPR39 overexpression could suppress oxidative stress, lipid accumulation and activate the SIRT1/Nrf2 signaling. GPR39 overexpression likewise alleviated mitochondrial dysfunction, whereas EX-527 treatment disturbed the effects of GPR39 overexpression on these aspects.

Conclusion: The present study found that GPR39 reduced oxidative stress and maintained mitochondrial homeostasis in a cellular model of NAFLD, a process mediated by SIRT1/Nrf2 signaling.