BACKGROUND In our previous studies, we prepared novel oligomannuronate-chromium(III) complexes (OM2, OM4) from marine alginate, and found that these compounds sensitize insulin action better than oligomannuronate(OM), chromium, and metformin in C2C12 skeletal muscle cells. In the present study, we studied their effects on mitochondrial biogenesis, lipid metabolism, and the underlying molecular ...

Malignant cells are subjected to high levels of oxidative stress that arise from the increased production of reactive oxygen species (ROS) due to their altered metabolism. They activate antioxidant mechanisms to relieve the oxidative stress, and thereby acquire resistance to chemotherapeutic agents. In the present study, we found that PGC1α, a key molecule that both increases mitochondrial biog...

BACKGROUND Inflammatory cytokines play an important role in the pathogenesis of heart failure. We have recently found the cytokine TWEAK (tumor necrosis factor (TNF)-like weak inducer of apoptosis), a member of the TNF superfamily, to be increased in patients with cardiomyopathy and result in the development of heart failure when overexpressed in mice. The molecular mechanisms underlying TWEAK-...

Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for INH-induced hepatotoxicity. In this study, we showed that INH impaired mitochon...

With one of the highest mitochondrial densities in the body, the kidneys consume approximately 10% of total oxygen while constituting 0.5% of body mass. Renal respiration is linear to solute extraction, linking oxidative metabolism directly to tubular function. This fundamental role of mitochondria in renal health may become an "Achilles heel" under duress. Acute kidney injury (AKI) related to ...

Orphan nuclear receptor ERRγ is a member of nuclear receptor superfamily that regulates several important cellular processes including hepatic glucose and alcohol metabolism. However, mechanistic understanding of transcriptional regulation of the ERRγ gene remains to be elucidated. Here, we report that activating transcription factor 6α (ATF6α), an endoplasmic reticulum (ER)-membrane-bound basi...

Purpose Photoreceptor degeneration in the retina is a major cause of blindness in humans. Elucidating mechanisms of degenerative and neuroprotective pathways in photoreceptors should afford identification and development of therapeutic strategies. Methods We used mouse genetic models and improved methods for retinal explant cultures. Retinas were enucleated from Mef2d+/+ and Mef2d-/- mice, st...

Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and p...

Abstract We have previously shown that mitochondrial dysfunction and disruption of biogenesis contribute to the pathogenesis IBD. Peroxisome Proliferator-activated Receptor–gamma Coactivator 1-alpha (PGC1α) is primary regulator biogenesis. In patients with ulcerative colitis (UC) mice undergoing experimental colitis, transcript protein levels PGC1α are reduced, which concomitant a decrease in f...