Tolerance to lipopolysaccharide (LPS) occurs when animals or cells exposed to LPS become hyporesponsive to a subsequent challenge with LPS. This mechanism is believed to be involved in the down-regulation of cellular responses observed in septic patients. The aim of this investigation was to evaluate LPS-induced monocyte tolerance of healthy volunteers using whole blood. The detection of intrac...

We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of t...

OBJECTIVE Activation of signal transducer and activator of transcription 3 (STAT3) was reported to be correlated with myocardial protection against ischemia/reperfusion (I/R) injury in ischemic preconditioning. Here, we tested the causality between STAT3 activity and cardioprotection. We also addressed the molecular mechanism for its cardioprotection. METHODS AND RESULTS Cardiac-specific tran...

BACKGROUND Ischemia and the following reperfusion damage are critical mechanisms of spinal cord injury. Statins have been reported to decrease ischemia-reperfusion injury in many organs including the spinal cord. Anti-oxidative effect is one of the main protective mechanisms of statin against neuronal death and cytotoxicity. We hypothesized that statins' anti-oxidative property would yield neur...

Extracellular signal regulated kinases (ERKs) are key regulatory proteins that mediate cell survival, proliferation and differentiation. Reactive oxygen species (ROS) may play a role in activation of the ERK pathway. Since mitochondria are a major source of ROS, we investigated whether mitochondrial-derived ROS play a role in ERK activation. Diazoxide, a potent mitochondrial ATP-sensitive K + c...

BACKGROUND/AIMS Inhibition of Drp-1-mediated mitochondrial fission limits reactive oxygen species (ROS) production and apoptosis in cardiomyocytes subjected to ischemia/reperfusion injury. It remains unknown if Dynamin 2 inhibition results in similar protective effects. Here we studied the role of Dynamin 2 in cardiomyocyte oxidative stress-induced apoptosis and ROS production. METHODS The ef...

Vitamin E, such as alpha-tocopherol (ATPH) and alpha-tocotrienol (ATTN), is a chain-breaking antioxidant that prevents the chain propagation step during lipid peroxidation. In the present study, we investigated the effects of ATTN on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC) and compared the neuroprotective effects of ATTN and ATPH. After 15 h KA (5 µM) treatm...

Zinc (Zn) deficiency is important for inducing nucleotide-binding domain and leucine‑rich repeat‑containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation in macrophages. However, its function in the NLRP3 inflammasome activation of peritoneal mesothelial cells (PMCs) remains to be elucidated. In the present study, the human PMC (HPMC) line HMrSV5 was co‑treated with high glu...

PURPOSE Quaternary ammonium ions have been demonstrated to induce apoptosis correlated with superoxide anion production in vitro. The purpose of this study was to further investigate the mechanisms of benzalkonium chloride (BAC), unpreserved and preserved beta-blocker eye-drops-induced programmed cell death, with special attention to the roles of mitochondrial transmembrane potential and intrac...

Mercury is a well-known toxic metal, which induces oxidative stress. Pancreatic beta-cells are vulnerable to oxidative stress. The pathophysiological effect of mercury on the function of pancreatic beta-cells remains unclear. The present study was designed to investigate the effects of methylmercury (MeHg)-induced oxidative stress on the cell viability and function of pancreatic beta-cells. The...