Pore water and solid-phase measurements on sediment cores from the Black Sea

The surface sediments in the Black Sea are underlain by extensive deposits of iron (Fe) oxide-rich lake sediments that were deposited prior to the inflow of marine Mediterranean Sea waters ca. 9000 years ago. The subsequent downward diffusion of marine sulfate into the methane-bearing lake sediments has led to a multitude of diagenetic reactions in the sulfate-methane transition zone (SMTZ), including anaerobic oxidation of methane (AOM) with sulfate. While the sedimentary cycles of sulfur (S), methane and Fe in the SMTZ have been extensively studied, relatively little is known about the diagenetic alterations of the sediment record occurring below the SMTZ. Here we combine detailed geochemical analyses of the sediment and pore water with multicomponent diagenetic modeling to study the diagenetic alterations below the SMTZ at two sites in the western Black Sea. We focus on the dynamics of Fe, S and phosphorus (P) and demonstrate that diagenesis has strongly overprinted the sedimentary burial records of these elements. Our results show that sulfate-mediated AOM substantially enhances the downward diffusive flux of sulfide into the deep limnic deposits. During this downward sulfidization, Fe oxides, Fe carbonates and Fe phosphates (e.g. vivianite) are converted to sulfide phases, leading to an enrichment in solid phase S and the release of phosphate to the pore water. Below the sulfidization front, high concentrations of dissolved ferrous Fe (Fe2+) lead to sequestration of downward diffusing phosphate as authigenic vivianite, resulting in a transient accumulation of total P directly below the sulfidization front. Our model results further demonstrate that downward migrating sulfide becomes partly re-oxidized to sulfate due to reactions with oxidized Fe minerals, fueling a cryptic S cycle and thus stimulating slow rates of sulfate-driven AOM (~ 1-100 pmol/cm**3/d) in the sulfate-depleted limnic deposits. However, this process is unlikely to explain the observed release of dissolved Fe2+ below the SMTZ. Instead, we suggest that besides organoclastic Fe oxide reduction, AOM coupled to the reduction of Fe oxides may also provide a possible mechanism for the high concentrations of Fe2+ in the pore water at depth. Our results reveal that methane plays a key role in the diagenetic alterations of Fe, S and P records in Black Sea sediments. The downward sulfidization into the limnic deposits is enhanced through sulfate-driven AOM with sulfate and AOM with Fe oxides may provide a deep source of dissolved Fe2+ that drives the sequestration of P in vivianite below the sulfidization front.

Preeclampsia : an accelerator–brake defect disorder

Life's perfect partnership starts with the placenta. If we get this right, we have the best chance of healthy life. In preeclampsia, we have a failing placenta. Preeclampsia kills one pregnant woman every minute and the life expectancy of those who survive is greatly reduced. Preeclampsia is treated roughly the same way it was when Thomas Edison was making the first silent movie. Globally, millions of women risk death to give birth each year and almost 300,000 lose their lives in this process. Over half a million babies around the world die each year as a consequence of preeclampsia. Despite decades of research, we lack pharmacological agents to treat it. Maternal endothelial dysfunction is a central phenomenon responsible for the clinical signs of preeclampsia. In the late nineties, we discovered that vascular endothelial growth factor (VEGF) stimulated nitric oxide release. This led us to suggest that preeclampsia arises due to the loss of VEGF activity, possibly due to a rise in soluble Flt-1 (sFlt-1), the natural antagonist of VEGF. Researchers have shown that high sFlt-1 elicits preeclampsia-like signs in pregnant rats and sFlt-1 increases before the clinical signs of preeclampsia in pregnant women. We demonstrated that removing or reducing this culprit protein from preeclamptic placenta restored the angiogenic balance. Heme oxygenase-1 (HO-1 or Hmox1) that generates carbon monoxide (CO), biliverdin (rapidly converted to bilirubin) and iron is cytoprotective. We showed that the Hmox1/CO pathway prevents human placental injury caused by pro-inflammatory cytokines and suppresses sFlt-1 and soluble endoglin release, factors responsible for preeclampsia phenotypes. The other key enzyme we identified is the hydrogen sulfide generating cystathionine-gamma-lyase (CSE or Cth). These are the only two enzyme systems shown to suppress sFlt-1 and to act as protective pathways against preeclampsia phenotypes in animal models. We also showed that when hydrogen sulfide restores placental vasculature, it also improves lagging fetal growth. These molecules act as the inhibitor systems in pregnancy and when they fail, this triggers preeclampsia. Discovering that statins induce these enzymes led us to an RCT to develop a low-cost therapy (StAmP Trial) to prevent or treat preeclampsia. If you think of pregnancy as a car then preeclampsia is an accelerator–brake defect disorder. Inflammation, oxidative stress and an imbalance in the angiogenic milieu fuel the ‘accelerator’. It is the failure in the braking systems (the endogenous protective pathway) that results in the ‘accelerator’ going out of control until the system crashes, manifesting itself as preeclampsia.

Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction

Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.

Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment

AIMS: Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vasculature by the enzyme cystathionine γ-lyase (CSE). However, the importance of CSE activity and local H2S generation for ischaemic vascular remodelling remains completely unknown. In this study, we examine the hypothesis that CSE critically regulates ischaemic vascular remodelling involving H2S-dependent mononuclear cell regulation of arteriogenesis. METHODS AND RESULTS: Arteriogenesis including mature vessel density, collateral formation, blood flow, and SPY angiographic blush rate were determined in wild-type (WT) and CSE knockout (KO) mice at different time points following femoral artery ligation (FAL). The role of endogenous H2S in regulation of IL-16 expression and subsequent recruitment of monocytes, and expression of VEGF and bFGF in ischaemic tissues, were determined along with endothelial progenitor cell (CD34/Flk1) formation and function. FAL of WT mice significantly increased CSE activity, expression and endogenous H2S generation in ischaemic tissues, and monocyte infiltration, which was absent in CSE-deficient mice. Treatment of CSE KO mice with the polysulfide donor diallyl trisulfide restored ischaemic vascular remodelling, monocyte infiltration, and cytokine expression. Importantly, exogenous H2S therapy restored nitric oxide (NO) bioavailability in CSE KO mice that was responsible for monocyte recruitment and arteriogenesis. CONCLUSION: Endogenous CSE/H2S regulates ischaemic vascular remodelling mediated during hind limb ischaemia through NO-dependent monocyte recruitment and cytokine induction revealing a previously unknown mechanism of arteriogenesis.

Oxygen tension, H2S, and NO bioavailability:is there an interaction?

Molecular oxygen (O2) is an essential component for survival and development. Variation in O2 levels leads to changes in molecular signaling and ultimately affects the physiological functions of many organisms. Nitric oxide (NO) and hydrogen sulfide (H2S) are two gaseous cellular signaling molecules that play key roles in several physiological functions involved in maintaining vascular homeostasis including vasodilation, anti-inflammation, and vascular growth. Apart from the aforementioned functions, NO and H2S are believed to mediate hypoxic responses and serve as O2 chemosensors in biological systems. In this literature review, we briefly discuss NO and H2S and their roles during hypoxia.

H2S regulation of nitric oxide metabolism

Nitric oxide (NO) and hydrogen sulfide (H2S) are two major gaseous signaling molecules that regulate diverse physiological functions. Recent publications indicate the regulatory role of H2S on NO metabolism. In this chapter, we discuss the latest findings on H2S-NO interactions through formation of novel chemical derivatives and experimental approaches to study these adducts. This chapter also addresses potential H2S interference on various NO detection techniques, along with precautions for analyzing biological samples from various sources. This information will facilitate critical evaluation and clearer insight into H2S regulation of NO signaling and its influence on various physiological functions.

Measurement of H2S in vivo and in vitro by the monobromobimane method

The gasotransmitter hydrogen sulfide (H2S) is known as an important regulator in several physiological and pathological responses. Among the challenges facing the field is the accurate and reliable measurement of hydrogen sulfide bioavailability. We have reported an approach to discretely measure sulfide and sulfide pools using the monobromobimane (MBB) method coupled with reversed phase high-performance liquid chromatography (RP-HPLC). The method involves the derivatization of sulfide with excess MBB under precise reaction conditions at room temperature to form sulfide dibimane (SDB). The resultant fluorescent SDB is analyzed by RP-HPLC using fluorescence detection with the limit of detection for SDB (2 nM). Care must be taken to avoid conditions that may confound H2S measurement with this method. Overall, RP-HPLC with fluorescence detection of SDB is a useful and powerful tool to measure biological sulfide levels.