Preservation Of Energy Metabolism Research Articles

Quantitative proteomics reveals Shexiang Baoxin Pill exerts cardioprotective effects by preserving energy metabolism in a rat model of myocardial infarction

Ethnopharmacological relevanceShexiang Baoxin Pill (SBP) is a composite formula of traditional Chinese medicine used to treat cardiovascular disease (CVD) in the clinic. However, the mechanism of its therapeutic effect on CVD has not been clearly elucidated yet. Aim of the studyThe aim of this study was to investigate the potential cardioprotective mechanism of SBP in the treatment of myocardial infarction (MI) model rats by applying proteomic approach. Materials and methodsThe rat model of MI was generated by ligating the left anterior descending coronary artery. Eighteen rats were randomly divided into three groups (n = 6 each): the MI group, MI group treated with SBP (SBP), and sham-operated group (SOG). Cardiac function in the experimental groups was assessed by echocardiography analyses after 15 days of treatment. A label-free quantitative proteomic approach was utilized to investigate the whole proteomes of heart tissues from the groups above on the day of the operation (Day 0) and 15 days later (Day 15). The differentially expressed proteins were subsequently analyzed with bioinformatic methods. Additionally, the expression levels of two promising proteins were validated by Western blotting. ResultsThe echocardiography analyses showed that SBP treatment significantly preserved the cardiac function of MI rats. Additionally, quantitative proteomics identified 389 differentially expressed proteins, and 15 proteins were considered as logical candidates for explaining the cardioprotective effect of SBP. Bioinformatic analysis of these differentially expressed proteins revealed that the proteins involved in cellular mitochondrial energy metabolism processes, such as fatty acid beta-oxidation and aerobic respiration, were significantly regulated under SBP treatment, of which fatty acid-binding protein 3 (FABP3) and myoglobin (MB) were significantly downregulated in the MI model group compared with the SOG group and returned to the basal level with SBP treatment, confirmed by Western blotting. ConclusionsThe results of our study suggest that the cardioprotective effects of SBP are achieved through the preservation of energy metabolism in the heart tissue of MI rats.

Possible mechanism of increasing resistance of the myocardium during combination of post infarction remodeling and diabetes mellitus

It was shown that the energy metabolism of the heart mitochondria of experimental animals and patients is more resistant to damage at combined postinfarction cardiosclerosis and diabetes in comparison with the individual pathology. We found that the changes of free fatty acid content and conjugation of the processes of oxidation and phosphorylation in heart mitochondria are components of the metabolic stability of myocardium at the combined development of postinfarction cardiosclerosis and diabetes mellitus. Our data demonstrate a direct link between the violations of the processes of oxidative phosphorylation and accumulation of free fatty acids owing to change in activity of endogenous phospholipases, in particularly, mi- tochondrial phospholipase A2. Similar results were obtained for intraoperative biopsy specimens of patients’ hearts, and of adult Wistar rats’ hearts. We hypothesized that the preservation of energy metabolism is a manifestation of summing up of compensatory processes at de- velopment of nonspecific response of cells to damage at the early stages of pathological pro- cess.

Liver ischemic preconditioning: a new strategy for the prevention of ischemia-reperfusion injury

Ischemic preconditioning renders the liver more tolerant to ischemia-reperfusion injury in warm and cold ischemia-reperfusion models. In general, the application of a 5 to 10-minute period of ischemia followed by 10 minutes of reperfusion confers early effective protection to the liver. Mechanisms responsible for this endogenous protective effect include: (1) transient nitric oxide production during liver preconditioning; (2) diminution of toxic reactive species generated on reperfusion; (3) remote effect on extrahepatic organs such as lung, kidney, and pancreas; (4) preservation of energy metabolism during ischemia; and (5) involvement of nuclear transcription factor and others.

Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection.

This review highlights recent advances in our understanding of mechanisms underlying reperfusion injury to the liver after warm hepatic ischemia. Sinusoidal endothelial cells and hepatocytes are targets of injury in the early 'cytotoxic' phase, although participation of apoptosis in the cell-death process remains contentious. Kupffer cells may play an important role as the initial cytotoxic cell type and are likely a source of reactive oxygen species and proinflammatory mediators, particularly tumor necrosis factor (TNF)-alpha. The latter are involved with subsequent neutrophil activation and recruitment. Microcirculatory disruption results from an imbalance between the actions of vasoconstrictors and vasodilators, such as nitric oxide, and also has a major impact on reperfusion injury. There is growing evidence that a brief prior ischemia-reperfusion period, termed 'ischemic preconditioning', is hepatoprotective. This can be mimicked by drugs that produce oxidative stress, and by interleukin-6 and TNF-alpha; both these cytokines are involved with priming hepatocytes to enter the cell cycle. Several mechanisms have been implicated including mobilization of adenosine and activation of adenosine type 2 receptors, nitric oxide, abrogation of TNF synthesis, preservation of energy metabolism, protection of the microcirculation and accelerated cell-cycle entry. A better understanding of preconditioning mechanisms will lead to novel approaches to improve outcomes of liver surgery.