Mitogen-activated protein kinases (MAPKs) are serine-threonine protein kinases that play the major role in signal transduction from the cell surface to the nucleus. MAPKs, which consist of growth factor-regulated extracellular signal-related kinases (ERKs), and the stress-activated MAPKs, c-jun NH2-terminal kinases (JNKs) and p38 MAPKs, are part of a three-kinase signaling module composed of the MAPK, an MAPK kinase (MAP2K) and an MAPK kinase (MAP3K). MAP3Ks phosphorylate MAP2Ks, which in turn activate MAPKs. MAPK phosphatases (MKPs), which recognize the TXY amino acid motif present in MAPKs, dephosphorylate and deactivate MAPKs. MAPK pathways are known to be influenced not only by receptor ligand interactions, but also by different stressors placed on the cell. One type of stress that induces potential activation of MAPK pathways is the oxidative stress caused by reactive oxygen species (ROS). Generally, increased ROS production in a cell leads to the activation of ERKs, JNKs, or p38 MAPKs, but the mechanisms by which ROS can activate these kinases are unclear. Oxidative modifications of MAPK signaling proteins and inactivation and/or degradation of MKPs may provide the plausible mechanisms for activation of MAPK pathways by ROS, which will be reviewed in this paper.
Growing evidence suggests that the elevation of free fatty acids, including palmitic acid (PA), are associated with inflammation and oxidative stress, which may be involved in endothelial dysfunction, characterized by the reduced bioavailability of nitric oxide (NO) synthesized from endothelial NO synthase (eNOS). Heme oxygenase-1 (HO-1) is important in the preservation of NO bioavailability. Piceatannol (Pic), with similar chemical structure to resveratrol, is suggested to possess similar protective effects as resveratrol. In the present study, human umbilical vein endothelial cells (HUVECs), stimulated with PA, were used to examine the endothelial protective effects of Pic. Pic increased the expression of HO-1 via nuclear factor erythroid-2-related factor-2 activation in the HUVECs, and decreased the PA-induced secretions of interleukin-6 and tumor necrosis factor-α, and the formation of reactive oxygen species ROS via inhibition of NF-κB activation. Notably, following inhibition of HO-1 activity by tin protoporphryin-IX, Pic did not prevent cytokine secretion, ROS formation, and NF-κB activation in the PA-stimulated HUVECs. PA attenuated insulin-mediated insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, leading to decreased glucose uptake, and phosphorylation of eNOS, leading to a reduction in the production of NO. Pic effectively mitigated the inhibitory effects of PA on the insulin-mediated phosphorylation of IRS-1 and eNOS, which was not observed following inhibition of HO-1 activity. The results of the present study suggested that Pic may have the potential to prevent PA-induced impairment of insulin signaling and eNOS function, by inducing the expression of the anti-inflammatory and antioxidant, HO-1.
Postherpetic neuralgia (PHN) is a disease entity defined as persistent pain after the acute pain of herpes zoster gradually resolves. It is associated with impaired daily activities, resulting in reduced quality of life. General epidemiological data on PHN is necessary for the effective management. However, data on the epidemiology of PHN in Korea is lacking. The aim of this study was to evaluate the epidemiological features of PHN in the general population.We used population-based medical data for 51,448,491 subscribers to the Health Insurance Service in the year of 2013 to analyze of PHN epidemiology in Korea, such as the incidence, regional distribution, seasonal variation, and healthcare resource utilization. Total number of patients and medical cost on PHN were analyzed from 2009 to 2013.Findings indicate that the incidence of PHN in Korea was 2.5 per 1000 person-years, which was strongly correlated with age and sex. There were no differences in seasonal variation or regional distribution. The medical cost increased steadily over the study period. When admitted to general hospitals, patients with PHN were mainly managed in the dermatology and anesthesiology departments.The incidence and prevalence rates of PHN in Koreans appear to be considerably higher compared to those in western populations, while the sex and age predisposition was similar. Considering that the pain associated with PHN can have a marked impact on a patient's quality of life resulting in a medicosocial economic burden, anesthesiology physicians have an important role in primary care in Korea. Future research on the cost-effectiveness of the management of PHN is needed.
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