Jubert Marquez

Echinochrome A Increases Mitochondrial Mass and Function by Modulating Mitochondrial Biogenesis Regulatory Genes

Echinochrome A (Ech A) is a natural pigment from sea urchins that has been reported to have antioxidant properties and a cardio protective effect against ischemia reperfusion injury. In this study, we ascertained whether Ech A enhances the mitochondrial biogenesis and oxidative phosphorylation in rat cardio myoblast H9c2 cells. To study the effects of Ech A on mitochondrial biogenesis, we measured mitochondrial mass, level of oxidative phosphorylation, and mitochondrial biogenesis regulatory gene expression. Ech A treatment did not induce cytotoxicity. However, Ech A treatment enhanced oxygen consumption rate and mitochondrial ATP level. Likewise, Ech A treatment increased mitochondrial contents in H9c2 cells. Furthermore, Ech A treatment up-regulated biogenesis of regulatory transcription genes, including proliferator-activated receptor gamma co-activator (PGC)-1α, estrogen-related receptor (ERR)-α, peroxisome proliferator-activator receptor (PPAR)-γ, and nuclear respiratory factor (NRF)-1 and such mitochondrial transcription regulatory genes as mitochondrial transcriptional factor A (TFAM), mitochondrial transcription factor B2 (TFB2M), mitochondrial DNA direct polymerase (POLMRT), single strand binding protein (SSBP) and Tu translation elongation factor (TUFM). In conclusion, these data suggest that Ech A is a potentiated marine drug which enhances mitochondrial biogenesis.

Effects of Various Patterns of Intermittent Hydrostatic Pressure on the Osteogenic Differentiation of Mesenchymal Stem Cells

This study investigated the effects of intemittent hydrostatic pressure (IHP) patterns on the responses of mesenchymal stem cells (MSCs) such as osteogenic differentiation, proliferation and senescence. For these experimental groups were set based on IHP patterns: (1) C_BM: control group with no stimulation in basal media; (2) C_OM: control group with no stimulation in osteogenic media (OM); (3) S_2H/5M: longer pressurizing (2hours) and shorter resting (5minutes) time in OM; (4) S_1H/1H: equal pressurizing and resting time (1hour) in OM; (5) S_2M/15M: shorter pressurizing (2minutes) and longer resting (15minutes) time in OM. The magnitude of IHP was 0.15 MPa. IHP was applied to corresponding groups for 4 hours a day from 3 days starting at 48 hours after seeding. Examination of DNA contents, ALP activity and its staining, quantitative real-time PCR, and β-galactosidase staining were performed. ALP amount normalized by corresponding DNA content in S_2H/5M, C_BM was significantly lower than that of the other group at day 5, which was more observable even at day 7 while S_2H/5M significantly had lower ALP count than other groups at day 5 and day 7. Other groups (S_1H/1H and S_2M/15M) showed significantly higher ALP amounts indicating the positive effect on osteogenic differentiation. Other markers indicating the degrees of differentiation showed comparable results. Based on β-galactosidase staining, it appeared that mechanical stimuli did not affect cell senescence significantly. From this study, we concluded that engagement of IHP has a potential of controlling osteogenic differentiation depending on its pattern: it can promote or suppress differentiation.

NecroX-5 protects mitochondrial oxidative phosphorylation capacity and preserves PGC1α expression levels during hypoxia/reoxygenation injury

Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment (10 µM) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC1α) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving PGC1α during cardiac HR injuries.

Post-Translational Modifications of Cardiac Mitochondrial Proteins in Cardiovascular Disease: Not Lost in Translation

Protein post-translational modifications (PTMs) are crucial in regulating cellular biology by playing key roles in processes such as the rapid on and off switching of signaling network and the regulation of enzymatic activities without affecting gene expressions. PTMs lead to conformational changes in the tertiary structure of protein and resultant regulation of protein function such as activation, inhibition, or signaling roles. PTMs such as phosphorylation, acetylation, and S-nitrosylation of specific sites in proteins have key roles in regulation of mitochondrial functions, thereby contributing to the progression to heart failure. Despite the extensive study of PTMs in mitochondrial proteins much remains unclear. Further research is yet to be undertaken to elucidate how changes in the proteins may lead to cardiovascular and metabolic disease progression in particular. We aimed to summarize the various types of PTMs that occur in mitochondrial proteins, which might be associated with heart failure. This study will increase the understanding of cardiovascular diseases through PTM.

Mitochondrial calcium uniporter inhibition attenuates mouse bone marrow-derived mast cell degranulation induced by beta-1,3-glucan

Mast cells are primary mediators of allergic inflammation. Beta-1,3-glucan (BG) protects against infection and shock by activating immune cells. Activation of the BG receptor induces an increase in intracellular Ca2+, which may induce exocytosis. However, little is known about the precise mechanisms underlying BG activation of immune cells and the possible role of mitochondria in this process. The present study examined whether BG induced mast cell degranulation, and evaluated the role of calcium transients during mast cell activation. Our investigation focused on the role of the mitochondrial calcium uniporter (MCU) in BG-induced degranulation. Black mouse (C57) bone marrow-derived mast cells were stimulated with 0.5 µg/ml BG, 100 µg/ml peptidoglycan (PGN), or 10 µM A23187 (calcium ionophore), and dynamic changes in cytosolic and mitochondrial calcium and membrane potential were monitored. BG-induced mast cell degranulation occurred in a time-dependent manner, and was significantly reduced under calcium-free conditions. Ruthenium red, a mitochondrial Ca2+ uniporter blocker, significantly reduced mast cell degranulation induced by BG, PGN, and A23187. These results suggest that the mitochondrial Ca2+ uniporter has an important regulatory role in BG-induced mast cell degranulation.

Rescue of Heart Failure by Mitochondrial Recovery

Heart failure (HF) is a multifactorial disease brought about by numerous, and oftentimes complex, etiological mechanisms. Although well studied, HF continues to affect millions of people worldwide and current treatments can only prevent further progression of HF. Mitochondria undoubtedly play an important role in the progression of HF, and numerous studies have highlighted mitochondrial components that contribute to HF. This review presents an overview of the role of mitochondrial biogenesis, mitochondrial oxidative stress, and mitochondrial permeability transition pore in HF, discusses ongoing studies that attempt to address the disease through mitochondrial targeting, and provides an insight on how these studies can affect future research on HF treatment.

You're Not under Arrest: Worry-free with β-arrestin

https://e-kcj.org Heart failure (HF) is a multi-factorial disease characterized by the inability of the heart to pump sufficient blood throughout the surrounding tissues. Scientific advances have recently aided in decreasing deaths attributed to HF; however, prevalence continues to increase as it threatens at least 26 million people globally.1) HF progression depends on several pre-existing conditions such as ischemic diseases like myocardial infarction (MI), eventually resulting in the death of cardiac cells. However, regeneration of cardiac cells in the adult heart is limited after injury and is instead replaced with a fibrotic scar. Therefore, researchers have resorted to stem cell therapy to restore these lost cells, and have demonstrated in numerous occasions the regenerative capabilities of cardiac progenitor cells (CPCs).2) CPCs can differentiate into various cell types including cardiomyocytes, and are capable of migration and tube formation, an important characteristic for developing therapies for ischemic myocardium.

Exercise-Induced Mitochondrial Adaptations in Addressing Heart Failure

Mitochondria are complex organelles essential for the production of energy. These dynamic, complex organelles found in every cell and tissues of the body have been well-studied in various physiological models, stressing that mitochondrial dysfunction is characteristic of pathological states, especially in cardiovascular diseases and heart failure. Since heart failure progresses due to energy deficits brought about by altered mitochondrial bioenergetics and functioning, novel ways of ameliorating mitochondrial dysfunction are being studied. Interestingly, various exercise modalities can serve as stimuli which can regulate the mitochondria in different ways, such as in the increase of mitochondrial mass and copy number, in the structural fusion and fission processes, and the removal of impaired mitochondria. Considering that there are numerous kinds and protocols for exercise, there are a number of ways exercise can affect the mitochondria as well. Nonetheless these processes affect each other to an extent, highlighting the pivotal role exercise plays in improving or enhancing the state of mitochondria during disease. This chapter will focus on how exercise of different can regulate mitochondrial processes, which could be used as therapeutic strategies in addressing heart failure.