Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells

<p>Abstract</p> <p>Background</p> <p>Vitamin K is essential for the posttranslational modification of various Gla proteins. Although it is widespread in several organs, including the testis, the function of vitamin K in these organs is not well characterized. In this study, we investigated the function of vitamin K in the testis and analyzed its role in steroidogenesis.</p> <p>Methods</p> <p>Eight-week-old male Wistar rats were fed a diet supplemented with menaquinone-4 (MK-4, 75 mg/kg diet), one of the predominant K₂vitamins present in the testis, for 5 weeks. <it>In vivo </it>testosterone levels of the rats' plasma and testes were measured by enzyme-linked immunosorbent assay, and <it>in vitro </it>testosterone levels of testis-derived tumor cells (I-10 cells) maintained in Ham's F-10 medium with 10% fetal bovine serum were measured following treatment with MK-4 (0 to 100 μM) at several time points. Testosterone and cellular protein levels were analyzed with respect to their effects on steroidogenesis.</p> <p>Results</p> <p>Testosterone levels in the plasma and testes of MK-4-fed rats were significantly increased compared to those of control rats, with no obvious differences in plasma luteinizing hormone levels. Secreted testosterone levels from I-10 cells were elevated by MK-4, but not by vitamin K₁, in a dose-dependent manner independent of cAMP treatment. Western blot analysis revealed that expression of CYP11A, the rate-limiting enzyme in steroidogenesis, and phosphorylation levels of protein kinase A (PKA) and the cAMP response element-binding protein were all stimulated by the presence of MK-4. Enhancement of testosterone production was inhibited by H89, a specific inhibitor of PKA, but not by warfarin, an inhibitor of γ-glutamylcarboxylation.</p> <p>Conclusions</p> <p>MK-4 stimulates testosterone production in rats and testis-derived tumor cells via activation of PKA. MK-4 may be involved in steroidogenesis in the testis, and its supplementation could reverse the downregulation of testosterone production in elders.</p

Cd, Hg, Pb, and As in European species of wild growing forest landscape fungi : a review

Kadmij (Cd), živo srebro (Hg), svinec (Pb) in arzen (As) so kovine, ki se naravno ali kot posledica človekove dejavnosti pojavljajo v okolju, tudi v gozdni krajini, kjer so rastišča številnih evropskih vrst gliv. Namen članka je bil pripraviti pregled vrst in količin izbranih kovin v trosnjakih gliv terprimerjati lastne raziskave, opravljene v različno onesnaženih območjih v Sloveniji (Zgornja Mežiška, Šaleška in Poljanska dolina), s podatki evropskih raziskav. Vsebnosti kovin v trosnjakih gliv iz neonesnaženih območij pravilomanajdemo v naslednjih intervalih: <0,5 mg/kg suhe teže (Cd), < 0,5 mg/kg do 10 mg/kg suhe teže (Hg), < 0,5 mg/kg do 5 mg/kg suhe teže (Pb) in < 0,5 mg/kg do 1 (2) mg/kg suhe teže (As). Na podlagi pregleda vsebnosti izbranih kovin v trosnjakih gliv ugotavljamo, da sta problematični kovini predvsem Cd in Hg. Omenjeni kovini lahko dosegata velike vsebnosti celo v glivah, ki rastejo v neonesnaženih območjih. Za vse analizirane kovin je značilno, da v trosnjakih gliv iz močno onesnaženih območji dosegajo velike, celo ekstemne vsebnosti, ki nekajkrat prekoračujejo vsebnosti iz neonesnaženih območij. Upoštevaje primerjavo z evropskimi raziskavami ugotavljamo, da je Zgornja Mežiška dolina obremenjena s Pb in Cd, Šaleška dolina pa s Cd in As.Metals, which originate from anthropogenic and natural activities, frequently occur in forest landscape with habitats of many European species of wild growing fungi. The presented review focuses on cadmium (Cd), mercury (Hg), lead (Pb), and arsenic (As) levels in fruiting bodies of wild growing European species of fungi of forest landscape. Furthermore, a comparison with studies of this kind performed in Slovenia was made with the aim to assess themetals levels in fungi from differently polluted areas in Slovenia (the Upper Meža Valley, the Šalek Valley, the Poljana Valley). The usual reported levels for most species grown in unpolluted areas are in the following ranges:Cd: < 0,5 mg/kg - 5 mg/kg dry weight (dw), Hg: < 0,5 mg/kg - 10 mg/kg dw, Pb: < 0,5 mg/kg - 5 mg/kg dw, As: < 0,5 mg/kg -1 (2) mg/kg dw (As), respectively. The presented data reveal that cadmium (Cd) and mercury (Hg) have probably been the most detrimental trace elements in fruiting bodies, which can reach increased levels even in unpolluted areas. It is evident for all analyzed trace elements that values can considerably increase in fungi picked in severely polluted areas. According to data regarding Slovene studies and comparison with other European studies, it is obvious that the Šalek Valley is enriched with Cd and As, while the Upper Meža Valley is considerably polluted with Pb and Cd

Carbon Monoxide Promotes Respiratory Hemoproteins Iron Reduction Using Peroxides as Electron Donors

The physiological role of the respiratory hemoproteins (RH), hemoglobin and myoglobin, is to deliver O2 via its binding to their ferrous (FeII) heme-iron. Under variety of pathological conditions RH proteins leak to blood plasma and oxidized to ferric (FeIII, met) forms becoming the source of oxidative vascular damage. However, recent studies have indicated that both metRH and peroxides induce Heme Oxygenase (HO) enzyme producing carbon monoxide (CO). The gas has an extremely high affinity for the ferrous heme-iron and is known to reduce ferric hemoproteins in the presence of suitable electron donors. We hypothesized that under in vivo plasma conditions, peroxides at low concentration can assist the reduction of metRH in presence of CO. The effect of CO on interaction of metRH with hydrophilic or hydrophobic peroxides was analyzed by following Soret and visible light absorption changes in reaction mixtures. It was found that under anaerobic conditions and low concentrations of RH and peroxides mimicking plasma conditions, peroxides served as electron donors and RH were reduced to their ferrous carboxy forms. The reaction rates were dependent on CO as well as peroxide concentrations. These results demonstrate that oxidative activity of acellular ferric RH and peroxides may be amended by CO turning on the reducing potential of peroxides and facilitating the formation of redox-inactive carboxyRH. Our data suggest the possible role of HO/CO in protection of vascular system from oxidative damage

Fruit fracture biomechanics and the release of Lepidium didymum pericarp-imposed mechanical dormancy by fungi

Mechanical dormancy imposed by a hard fruit pericarp prevents premature seed germination. Here, the authors show that the pericarp of Lepidium didymum prevents germination by limiting water uptake and that dormancy can be released by fungal activity that weakens predetermined breaking zones in the fruit coat

Signatures of a globally optimal searching strategy in the three-dimensional foraging flights of bumblebees

Simulated annealing is a powerful stochastic search algorithm for locating a global maximum that is hidden among many poorer local maxima in a search space. It is frequently implemented in computers working on complex optimization problems but until now has not been directly observed in nature as a searching strategy adopted by foraging animals. We analysed high-speed video recordings of the three-dimensional searching flights of bumblebees (Bombus terrestris) made in the presence of large or small artificial flowers within a 0.5 m3 enclosed arena. Analyses of the three-dimensional flight patterns in both conditions reveal signatures of simulated annealing searches. After leaving a flower, bees tend to scan back-and forth past that flower before making prospecting flights (loops), whose length increases over time. The search pattern becomes gradually more expansive and culminates when another rewarding flower is found. Bees then scan back and forth in the vicinity of the newly discovered flower and the process repeats. This looping search pattern, in which flight step lengths are typically power-law distributed, provides a relatively simple yet highly efficient strategy for pollinators such as bees to find best quality resources in complex environments made of multiple ephemeral feeding sites with nutritionally variable rewards

Loss of Cofilin 1 Disturbs Actin Dynamics, Adhesion between Enveloping and Deep Cell Layers and Cell Movements during Gastrulation in Zebrafish

During gastrulation, cohesive migration drives associated cell layers to the completion of epiboly in zebrafish. The association of different layers relies on E-cadherin based cellular junctions, whose stability can be affected by actin turnover. Here, we examined the effect of malfunctioning actin turnover on the epibolic movement by knocking down an actin depolymerizing factor, cofilin 1, using antisense morpholino oligos (MO). Knockdown of cfl1 interfered with epibolic movement of deep cell layer (DEL) but not in the enveloping layer (EVL) and the defect could be specifically rescued by overexpression of cfl1. It appeared that the uncoordinated movements of DEL and EVL were regulated by the differential expression of cfl1 in the DEL, but not EVL as shown by in situ hybridization. The dissociation of DEL and EVL was further evident by the loss of adhesion between layers by using transmission electronic and confocal microscopy analyses. cfl1 morphants also exhibited abnormal convergent extension, cellular migration and actin filaments, but not involution of hypoblast. The cfl1 MO-induced cell migration defect was found to be cell-autonomous in cell transplantation assays. These results suggest that proper actin turnover mediated by Cfl1 is essential for adhesion between DEL and EVL and cell movements during gastrulation in zebrafish