Role of histamine receptors in the effects of histamine on the production of reactive oxygen species by whole blood phagocytes

Aims

The diverse physiological functions of histamine are mediated through distinct histamine receptors. In this study we investigated the role of H₂R and H₄R in the effects of histamine on the production of reactive oxygen species by phagocytes in whole blood.

Main methods

Changes in reactive oxygen species (ROS) production by whole blood phagocytes after treatment with histamine, H₄R agonists (4-methylhistamine, VUF8430), H₂R agonist (dimaprit) and their combinations with H₄R antagonist (JNJ10191584) and H₂R antagonist (ranitidine) were determined using the chemiluminescence (CL) assay. To exclude the direct scavenging effects of the studied compounds on the CL response, the antioxidant properties of all compounds were measured using several methods (TRAP, ORAC, and luminol–HRP–H₂O₂ based CL).

Key findings

Histamine, 4-methylhistamine, VUF8430 and dimaprit inhibited the spontaneous and OZP-activated whole blood CL in a dose-dependent manner. On the other hand, only VUF8430 was able to inhibit PMA-activated whole blood CL. Ranitidine, but not JNJ10191584, completely reduced the effects of histamine, 4-methylhistamine and dimaprit. The direct scavenging ability of tested compounds was negligible.

Significance

Our results demonstrate that the inhibitory effects of histamine on ROS production in whole blood phagocytes were caused by H₂R. Our results also suggest that H₄R agonists in concentrations higher than 10^− 6 M may also influence ROS production via binding to H₂R.     

Inositol 1,4,5-trisphosphate receptor-isoform diversity in cell death and survival

Cell-death and -survival decisions are critically controlled by intracellular Ca^2 + homeostasis and dynamics at the level of the endoplasmic reticulum (ER). Inositol 1,4,5-trisphosphate (IP₃) receptors (IP₃Rs) play a pivotal role in these processes by mediating Ca^2 + flux from the ER into the cytosol and mitochondria. Hence, it is clear that many pro-survival and pro-death signaling pathways and proteins affect Ca^2 + signaling by directly targeting IP₃R channels, which can happen in an IP₃R-isoform-dependent manner. In this review, we will focus on how the different IP₃R isoforms (IP₃R1, IP₃R2 and IP₃R3) control cell death and survival. First, we will present an overview of the isoform-specific regulation of IP₃Rs by cellular factors like IP₃, Ca^2 +, Ca^2 +-binding proteins, adenosine triphosphate (ATP), thiol modification, phosphorylation and interacting proteins, and of IP₃R-isoform specific expression patterns. Second, we will discuss the role of the ER as a Ca^2 + store in cell death and survival and how IP₃Rs and pro-survival/pro-death proteins can modulate the basal ER Ca^2 + leak. Third, we will review the regulation of the Ca^2 +-flux properties of the IP₃R isoforms by the ER-resident and by the cytoplasmic proteins involved in cell death and survival as well as by redox regulation. Hence, we aim to highlight the specific roles of the various IP₃R isoforms in cell-death and -survival signaling. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.     

Soil water use strategy of dominant species in typical natural and planted shrubs in loess hilly region

Aims Artemisia gmelinii is a dominant specie naturally established after abandonment of cultivated lands in the Loess Plateau, and Caragana korshinskii is one of the main planted shrub species to control soil erosion. Improved understanding of water use strategies of these two species is of great significance to evaluate the sustainable development of the Loess Plateau under the trend of climate warming and increasing drought events.
Methods Stable oxygen-18 isotope was used to determine seasonal variations in the water sources of native A. gmelinii communities established after abandonment of cultivated lands for 7 and 30 years and planted C. korshinskii after 30 years. The contributions of soil water from different depths to water uptake were estimated by the MixSIR Bayesian mixing model. The geometric mean regression method was used to fit the line of precipitation to get the local meteoric water line (LWML).
Important findings The stable hydrogen isotope rate (δD) and stable oxygen isotope rate (δ¹⁸O) of soil water and xylem water plotted to the right side of the LWML, indicating that the isotopic compositions of soil water were enriched due to evaporation. The native A. gmelinii communities established after abandonment of cultivated lands for 7 years and planted C. korshinskii after 30 years showed plasticity in switching water sources from different soil layers, extracting water from shallow soil (0-40 cm) when soil water was available, but deeper soil (40-80 cm) when shallow soil water was dry. In contrast, A. gmelinii growing in site after cultivation abandonment for 30 years mainly relied on water from the surface soil (0-10 cm) throughout the growing season. Our results suggest that the ability of A. gmelinii to compete for soil water reduces with aging of the community while the planted C. korshinskii will have competitive advantage under the condition of increasing frequency of drought events in the future.     

Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H₂O₂) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H₂O₂-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.     

Hypoxia induces beta-amyloid in association with death of RGC-5 cells in culture

Beta-amyloid (Aβ) derived from amyloid precursor protein (APP) has been associated with retinal degeneration in Alzheimer’s disease (AD) and glaucoma. This study examined whether hypoxia exposure induces Aβ accumulation in RGC-5 cells. While levels of APP mRNA and protein significantly increased in the cells, elevated abundance of Aβ was also observed in cells and culture medium between 12 or 24 and 48 h after 5% O₂ hypoxia treatment. Additionally, there is a close relationship between induction of APP and Aβ and intracellular accumulation of ROS along with loss of mitochondrial membrane potential followed by the death of RGC-5 cells in culture under hypoxia. These results suggest a possible involvement of APP and Aβ in the death of RGCs challenged by hypoxia.     

Effect of thymol on peripheral blood mononuclear cell PBMC and acute promyelotic cancer cell line HL-60

Thymol, a naturally occurring phenolic compound, has been known for its antioxidant, anti microbial, and anti inflammatory activity. Thymol has also been reported as anti-cancer agent, but its anti-cancer mechanism has not yet been fully elucidated. Thus, we aimed to investigate anticancer activity of thymol on HL-60 (acute promyelotic leukemia) cells. In our study, thymol demonstrated dose dependent cytotoxic effects on HL-60 cells after 24 h of exposure. However, thymol did not show any cytotoxic effect in normal human PBMC. The cytotoxic effect of thymol on HL-60 cells appears to be associated with induction of cell cycle arrest at sub G0/G1 phase, and apoptotic cell death based on genomic DNA fragmentation pattern. Thymol also showed significant increase in production of reactive oxygen species (ROS) activity, increase in mitochondrial H₂O₂ production and depolarization of mitochondrial membrane potential. On performing Western Blot analysis, thymol showed increase in Bax protein level with a concomitant decrease in Bcl2 protein expression in a dose dependent manner. Our study also showed activation of caspase -9, -8 and -3 and concomitant PARP cleavage, which is the hallmark of caspase-dependent apoptosis. Moreover, to rule out the involvement of other mechanisms in apoptosis induction by thymol, we also studied its effect on apoptosis inducing factor (AIF). Thymol induced AIF translocation from mitochondria to cytosol and to nucleus, thus indicating its ability to induce caspase independent apoptosis. We conclude that, thymol-induced apoptosis in HL-60 cells involves both caspase dependent and caspase independent pathways.     

Excess irradiance causes early symptoms of senescence during leaf expansion in photoautotrophically <Emphasis Type="Italic">in vitro</Emphasis> grown tobacco plants

Photosynthetic parameters, growth, and pigment contents were determined during expansion of the fourth leaf of in vitro photoautotrophically cultured Nicotiana tabacum L. plants at three irradiances [photosynthetically active radiation (400–700 nm): low, LI 60 μmol m⁻² s⁻¹; middle, MI 180 μmol m⁻² s⁻¹; and high, HI 270 μmol m⁻² s⁻¹]. During leaf expansion, several symptoms usually accompanying leaf senescence appeared very early in HI and then in MI plants. Symptoms of senescence in developing leaves were: decreasing chlorophyll (Chl) a+b content and Chl a/b ratio, decreasing both maximum (F_V/F_M) and actual (Φ_PS2) photochemical efficiency of photosystem 2, and increasing non-photochemical quenching. Nevertheless, net photosynthetic oxygen evolution rate (P _N) did not decrease consistently with decrease in Chl content, but exhibited a typical ontogenetic course with gradual increase. P _N reached its maximum before full leaf expansion and then tended to decline. Thus excess irradiance during in vitro cultivation did not cause early start of leaf senescence, but impaired photosynthetic performance and Chl content in leaves and changed their typical ontogenetic course.