University of Hawaii at Manoa

About: University of Hawaii at Manoa is a education organization based out in Honolulu, Hawaii, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 13693 authors who have published 25161 publications receiving 1023924 citations.

TRPM2: a multifunctional ion channel for calcium signalling

Abstract: The transient potential receptor melastatin-2 (TRPM2) channel has emerged as an important Ca(2+) signalling mechanism in a variety of cells, contributing to cellular functions that include cytokine production, insulin release, cell motility and cell death. Its ability to respond to reactive oxygen species has made TRPM2 a potential therapeutic target for chronic inflammation, neurodegenerative diseases, and oxidative stress-related pathologies. TRPM2 is a non-selective, calcium (Ca(2+))-permeable cation channel of the melastatin-related transient receptor potential (TRPM) ion channel subfamily. It is activated by intracellular adenosine diphosphate ribose (ADPR) through a diphosphoribose hydrolase domain in its C-terminus and regulated through a variety of factors, including synergistic facilitation by [Ca(2+)](i), cyclic ADPR, H(2)O(2), NAADP, and negative feedback regulation by AMP and permeating protons (pH). In addition to its role mediating Ca(2+) influx into the cells, TRPM2 can also function as a lysosomal Ca(2+) release channel, contributing to cell death. The physiological and pathophysiological context of ROS-mediated events makes TRPM2 a promising target for the development of therapeutic tools of inflammatory and degenerative diseases.

Oxidative Stress and Inflammation in Heart Disease: Do Antioxidants Have a Role in Treatment and/or Prevention?

Abstract: Inflammation triggered by oxidative stress is the cause of much, perhaps even most, chronic human disease including human aging. The oxidative stress originates mainly in mitochondria from reactive oxygen and reactive nitrogen species (ROS/RNS) and can be identified in most of the key steps in the pathophysiology of atherosclerosis and the consequential clinical manifestations of cardiovascular disease. In addition to the formation of atherosclerosis, it involves lipid metabolism, plaque rupture, thrombosis, myocardial injury, apoptosis, fibrosis and failure. The recognition of the critical importance of oxidative stress has led to the enthusiastic use of antioxidants in the treatment and prevention of heart disease, but the results of prospective, randomized clinical trials have been overall disappointing. Can this contradiction be explained and what are its implications for the discovery/development of future antioxidant therapeutics?

Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation

Abstract: Asbestos carcinogenesis has been linked to the release of cytokines and mutagenic reactive oxygen species (ROS) from inflammatory cells. Asbestos is cytotoxic to human mesothelial cells (HM), which appears counterintuitive for a carcinogen. We show that asbestos-induced HM cell death is a regulated form of necrosis that links to carcinogenesis. Asbestos-exposed HM activate poly(ADP-ribose) polymerase, secrete H2O2, deplete ATP, and translocate high-mobility group box 1 protein (HMGB1) from the nucleus to the cytoplasm, and into the extracellular space. The release of HMGB1 induces macrophages to secrete TNF-α, which protects HM from asbestos-induced cell death and triggers a chronic inflammatory response; both favor HM transformation. In both mice and hamsters injected with asbestos, HMGB1 was specifically detected in the nuclei, cytoplasm, and extracellular space of mesothelial and inflammatory cells around asbestos deposits. TNF-α was coexpressed in the same areas. HMGB1 levels in asbestos-exposed individuals were significantly higher than in nonexposed controls (P < 0.0001). Our findings identify the release of HMGB1 as a critical initial step in the pathogenesis of asbestos-related disease, and provide mechanistic links between asbestos-induced cell death, chronic inflammation, and carcinogenesis. Chemopreventive approaches aimed at inhibiting the chronic inflammatory response, and especially blocking HMGB1, may decrease the risk of malignant mesothelioma among asbestos-exposed cohorts.

Interdecadal Changes in the Major Modes of Asian–Australian Monsoon Variability: Strengthening Relationship with ENSO since the Late 1970s*

Abstract: The present paper develops an integral view of the year-to-year variability across the entire Asian–Australian monsoon (A–AM) system, which covers one-third of the global tropics between 40° and 160°E. Using season-reliant empirical orthogonal function (S-EOF) analysis, the authors identified two major modes of variability for the period 1956–2004. The first exhibits a prominent biennial tendency and concurs with the turnabout of El Nino–Southern Oscillation (ENSO), providing a new perspective of the seasonally evolving spatiotemporal structure for tropospheric biennial oscillation. The second mode leads ENSO by one year. The remote El Nino forcing, the monsoon–warm pool ocean interaction, and the influence of the annual cycle are three fundamental factors for understanding the behavior of the first mode. The monsoon–ocean interaction is characterized by a positive feedback between the off-equatorial convectively coupled Rossby waves and the underlying sea surface temperature (SST) “dipole” anoma...