On the chemical biology of the nitrite/sulfide interaction

The authors are grateful to the Susanne-Bunnenberg-Stiftung of the Düsseldorf Heart Center (to MK), the COST action BM1005 (European Network on Gasotransmitters), and the Faculty of Medicine, University of Southampton (to MF) for financial support.Sulfide (H2S/HS−) has been demonstrated to exert an astounding breadth of biological effects, some of which resemble those of nitric oxide (NO). While the chemistry, biochemistry and potential pathophysiology of the cross-talk between sulfide and NO have received considerable attention lately, a comparable assessment of the potential biological implications of an interaction between nitrite and sulfide is lacking. This is surprising inasmuch as nitrite is not only a known bioactive oxidation product of NO, but also efficiently converted to S-nitrosothiols in vivo; the latter have been shown to rapidly react with sulfide in vitro, leading to formation of S/N-hybrid species including thionitrite (SNO−) and nitrosopersulfide (SSNO−). Moreover, nitrite is used as a potent remedy against sulfide poisoning in the clinic. The chemistry of interaction between nitrite and sulfide or related bioactive metabolites including polysulfides and elemental sulfur has been extensively studied in the past, yet much of this information appears to have been forgotten. In this review, we focus on the potential chemical biology of the interaction between nitrite and sulfide or sulfane sulfur molecules, calling attention to the fundamental chemical properties and reactivities of either species and discuss their possible contribution to the biology, pharmacology and toxicology of both nitrite and sulfide.Publisher PDFPeer reviewe

Anomalies in a waterlike model confined between plates

Using molecular dynamic simulations we study a waterlike model confined between two fixed hydrophobic plates. The system is tested for density, diffusion and structural anomalous behavior and compared with the bulk results. Within the range of confining distances we had explored we observe that in the pressure-temperature phase diagram the temperature of maximum density (TMD line), the temperature of maximum and minimum diffusion occur at lower temperatures when compared with the bulk values. For distances between the two layers below a certain threshold ,$d\le d_c$, only two layers of particles are formed, for $d\ge d_c$ three or more layers are formed. In the case of three layers the central layer stays liquid while the contact layers crystallize. This result is in agreement with simulations for atomistic models

Decentralization Policy and The Struggle for Authority Over Forest Resources in Tebo Regency, Jambi

Kebijakan desentralisasi atau yang umum dikenal dengan istilah otonomi daerah mengamanatkan kepada pusat untuk menyerahkan berbagai kewenangan pemerintahan kepadadaerah. Penyerahan kewenangan kepada daerah ini dimaksudkan agar tata pemerintahan dan pelayanan publik dapat berjalan secara lebih efektif dan efisien. Namun, peralihan sistem pemerintahan dari sentralisasi ke desentralisasi tidak selamanya berjalan lurus mulus. Ketegangan hubungan pusat dan daerah terjadi akibat keengganan penyelenggara pemerintahan di tingkat pusatmenyerahkan kewenangan kepada daerah dan egoisme kedaerahan yang berlebihan ditandai dengan terbitnya berbagai Peraturan Daerah yang bertentangan dengan peraturan di atasnya. Hal ini mengakibatkan ketidakpastian hukum yang berpotensi memicu konflik antara pusat dan daerah serta antara kelompok masyarakat menyangkut hak mereka untuk mendapatkan manfaat, akses dan tanggung jawab atas sumber daya alam termasuk huta

Nitrosopersulfide (SSNO(-)) targets the Keap-1/Nrf2 redox system.

Nitric oxide (NO), hydrogen sulfide and polysulfides have been proposed to contribute to redox signaling by activating the Keap-1/Nrf2 stress response system. Nitrosopersulfide (SSNO(-)) recently emerged as a bioactive product of the chemical interaction of NO or nitrosothiols with sulfide; upon decomposition it generates polysulfides and free NO, triggering the activation of soluble guanylate cyclase, inducing blood vessel relaxation in vitro and lowering blood pressure in vivo. Whether SSNO(-) itself interacts with the Keap-1/Nrf2 system is unknown. We therefore sought to investigate the ability of SSNO(-) to activate Nrf2-dependent processes in human vascular endothelial cells, and to compare the pharmacological effects of SSNO(-) with those of its precursors NO and sulfide at multiple levels of target engagement. We here demonstrate that SSNO(-) strongly increases Nrf2 nuclear levels, Nrf2-binding activity and transactivation activity, thereby increasing mRNA expression of Hmox-1, the gene encoding for heme oxygenase 1, without adversely affecting cell viability. Under all conditions, SSNO(-) appeared to be more potent than its parent compounds, NO and sulfide. SSNO(-)-induced Nrf2 transactivation activity was abrogated by either NO scavenging with cPTIO or inhibition of thiol sulfuration by high concentrations of cysteine, implying a role for both persulfides/polysulfides and NO in SSNO(-) mediated Nrf2 activation. Taken together, our studies demonstrate that the Keap-1/Nrf2 redox system is a biological target of SSNO(-), enriching the portfolio of bioactivity of this vasoactive molecule to also engage in the regulation of redox signaling processes. The latter suggests a possible role as messenger and/or mediator in cellular sensing and adaptations processes

The adaptor protein PID1 regulates receptor-dependent endocytosis of postprandial triglyceride-rich lipoproteins.

ObjectiveInsulin resistance is associated with impaired receptor dependent hepatic uptake of triglyceride-rich lipoproteins (TRL), promoting hypertriglyceridemia and atherosclerosis. Next to low-density lipoprotein (LDL) receptor (LDLR) and syndecan-1, the LDLR-related protein 1 (LRP1) stimulated by insulin action contributes to the rapid clearance of TRL in the postprandial state. Here, we investigated the hypothesis that the adaptor protein phosphotyrosine interacting domain-containing protein 1 (PID1) regulates LRP1 function, thereby controlling hepatic endocytosis of postprandial lipoproteins.MethodsLocalization and interaction of PID1 and LRP1 in cultured hepatocytes was studied by confocal microscopy of fluorescent tagged proteins, by indirect immunohistochemistry of endogenous proteins, by GST-based pull down and by immunoprecipitation experiments. The in vivo relevance of PID1 was assessed using whole body as well as liver-specific Pid1-deficient mice on a wild type or Ldlr-deficient (Ldlr-/-) background. Intravital microscopy was used to study LRP1 translocation in the liver. Lipoprotein metabolism was investigated by lipoprotein profiling, gene and protein expression as well as organ-specific uptake of radiolabelled TRL.ResultsPID1 co-localized in perinuclear endosomes and was found associated with LRP1 under fasting conditions. We identified the distal NPxY motif of the intracellular C-terminal domain (ICD) of LRP1 as the site critical for the interaction with PID1. Insulin-mediated NPxY-phosphorylation caused the dissociation of PID1 from the ICD, causing LRP1 translocation to the plasma membrane. PID1 deletion resulted in higher LRP1 abundance at the cell surface, higher LDLR protein levels and, paradoxically, reduced total LRP1. The latter can be explained by higher receptor shedding, which we observed in cultured Pid1-deficient hepatocytes. Consistently, PID1 deficiency alone led to increased LDLR-dependent endocytosis of postprandial lipoproteins and lower plasma triglycerides. In contrast, hepatic PID1 deletion on an Ldlr-/- background reduced lipoprotein uptake into liver and caused plasma TRL accumulation.ConclusionsBy acting as an insulin-dependent retention adaptor, PID1 serves as a regulator of LRP1 function controlling the disposal of postprandial lipoproteins. PID1 inhibition provides a novel approach to lower plasma levels of pro-atherogenic TRL remnants by stimulating endocytic function of both LRP1 and LDLR in the liver

Mental contrasting spurs energy by changing implicit evaluations of obstacles

Mentally contrasting a desired future with the obstacle of current reality produces expectancy-dependent changes in explicit evaluations of the obstacle of current reality. Past research has shown that these changes at least partly mediate the beneficial effects of mental contrasting on performance. We tested whether mental contrasting also leads to expectancy-dependent changes in implicit evaluations of the obstacle and whether those changes mediate mental contrasting effects on energization and performance. In 3 studies, participants named a desired future (improving interpersonal relationships, Study 1; excelling in a creativity test, Study 2; and improving one’s eating habits, Study 3) and named an important obstacle standing in the way of attaining the desired future. They then engaged in either mental contrasting or control exercises. We assessed participants’ implicit evaluations of their obstacles. Participants in the mental contrasting (vs. control) conditions implicitly evaluated their obstacles more negatively when they had high expectations of success (Studies 1, 2, and 3). Furthermore, expectancy-dependent changes in implicit evaluations of obstacles (i.e., food temptations) mediated mental contrasting effects on energization, which, in turn, predicted commitment and performance (i.e., commitment to eat healthily and healthy eating over the course of 2 weeks, Study 3)

Decentralization Policy and The Struggle for Authority Over Forest Resources in Tebo Regency, Jambi

Kebijakan desentralisasi atau yang umum dikenal dengan istilah otonomi daerah mengamanatkan kepada pusat untuk menyerahkan berbagai kewenangan pemerintahan kepadadaerah. Penyerahan kewenangan kepada daerah ini dimaksudkan agar tata pemerintahan dan pelayanan publik dapat berjalan secara lebih efektif dan efisien. Namun, peralihan sistem pemerintahan dari sentralisasi ke desentralisasi tidak selamanya berjalan lurus mulus. Ketegangan hubungan pusat dan daerah terjadi akibat keengganan penyelenggara pemerintahan di tingkat pusatmenyerahkan kewenangan kepada daerah dan egoisme kedaerahan yang berlebihan ditandai dengan terbitnya berbagai Peraturan Daerah yang bertentangan dengan peraturan di atasnya. Hal ini mengakibatkan ketidakpastian hukum yang berpotensi memicu konflik antara pusat dan daerah serta antara kelompok masyarakat menyangkut hak mereka untuk mendapatkan manfaat, akses dan tanggung jawab atas sumber daya alam termasuk huta

On the chemical biology of the nitrite/sulfide interaction

Sulfide (H2S/HS(-)) has been demonstrated to exert an astounding breadth of biological effects, some of which resemble those of nitric oxide (NO). While the chemistry, biochemistry and potential (patho)physiology of the cross-talk between sulfide and NO has received considerable attention lately, a comparable assessment of the potential biological implications of an interaction between nitrite and sulfide is lacking. This is surprising inasmuch as nitrite is not only a known bioactive oxidation product of NO, but also efficiently converted to S-nitrosothiols in vivo; the latter have been shown to rapidly react with sulfide in vitro, leading to formation of S/N-hybrid species including thionitrite (SNO(-)) and nitrosopersulfide (SSNO(-)). Moreover, nitrite is used as a potent remedy against sulfide poisoning in the clinic. The chemistry of interaction between nitrite and sulfide or related bioactive metabolites including polysulfides and elemental sulfur has been extensively studied in the past, yet much of this information appears to have been forgotten. In this review, we focus on the potential chemical biology of the interaction between nitrite and sulfide or sulfane sulfur molecules, calling attention to the fundamental chemical properties and reactivity of either species and discuss its possible contribution to the biology, pharmacology and toxicology of both nitrite and sulfide