Role of Intracellular Labile Zinc in LPS-Induced Apoptosis in Sheep Pulmonary Arterial Endothelial Cells (SPAECS)

We recently noted that exogenous zinc was capable of counteracting LPS-induced decreases in labile [Zn]i (i.e., TPEN chelatable, FluoZin-3 detectable) and simultaneously abrogated LPS-induced apoptosis in SPAECs. In an abbreviated survey of the effect of LPS on potential zinc transporters, we noted that LPS increased mRNA of zinc importer, SLC39A14 or ZIP14 (and this effect was mimicked by zinc chelator, TPEN) suggesting that increased expression of SLC39A14 may be an homeostatic mechanism to maintain [Zn]i and reduce cellular toxicity to LPS. In the current study, we noted that knockdown of SLC39A14 with siRNA rendered SPAECs more sensitive to LPS-induced apoptosis and also impaired the ability of exogenous zinc to rescue this effect. We also previously noted that iNOS or chemically derived (S-nitroso-N-acetylpenicillamine (SNAP)) nitric oxide (NO) is associated with resistant phenotype to LPS-induced apoptosis in a zinc dependent fashion. Since ZIP14 expression has been reported to be indirectly upregulated by NO, we pursued this connection in SPAECs by silencing ZIP14 using siRNA technology. We noted that NO-mediated resistance to LPS-induced apoptosis was independent of ZIP14 but was critically dependent upon the presence of sheep metallothionein (MT). In particular, genetic silencing of these collective forms of sheep MT isoforms abrogated the NO-dependent resistant phenotype to LPS-induced apoptosis as well as abolishing NO-mediated increases in [Zn]i. Collectively, these data confirm that increases in labile [Zn]i are an important component of ZIP14- or NO-mediated resistance to LPS-induced apoptosis. Cytoprotection via ZIP14 appears to be secondary to transcellular movement of extracellular zinc whereas NO mediated protection is secondary to S-nitrosation of MT and redistribution of intracellular zinc

Existence, Uniqueness and Stability of Fractional Order Stochastic Delay System

This chapter deals with the problem of fractional higher-order stochastic delay systems. A solution representation is given by using sin and cos matrix functions for different delay intervals. Further, existence and uniqueness results are proved through fixed point theorem. Moreover, finite-time stability criteria are obtained using fractional Gronwall-Bellman inequality lemma. Finally, numerical simulation is carried out to check the proposed theoretical results

Zinc homeostasis and signaling in health and diseases: Zinc signaling

The essential trace element zinc (Zn) is widely required in cellular functions, and abnormal Zn homeostasis causes a variety of health problems that include growth retardation, immunodeficiency, hypogonadism, and neuronal and sensory dysfunctions. Zn homeostasis is regulated through Zn transporters, permeable channels, and metallothioneins. Recent studies highlight Zn’s dynamic activity and its role as a signaling mediator. Zn acts as an intracellular signaling molecule, capable of communicating between cells, converting extracellular stimuli to intracellular signals, and controlling intracellular events. We have proposed that intracellular Zn signaling falls into two classes, early and late Zn signaling. This review addresses recent findings regarding Zn signaling and its role in physiological processes and pathogenesis

Induction of systemic resistance in rice by leaf extracts of Zizyphus jujuba and Ipomoea carnea against Rhizoctonia solani

Plants accumulate a great diversity of natural products, many of which confer protective effects against phytopathogenic attack. Earlier we had demonstrated that the leaf extracts of Zizyphus jujuba and Ipomoea carnea inhibit the in vitro mycelial growth of Rhizoctonia solani, and effectively reduce the incidence of sheath blight disease in rice.7 Here we demonstrate that foliar application of the aqueous leaf extracts of Z. jujuba and I. carnea followed by challenge inoculation with R. solani induces systemic resistance in rice as evident from significantly increased accumulation of pathogenesis-related proteins such as chitinase, β-1,3-glucanase and peroxidase, as well as defense-related compounds such as phenylalanine ammonia-lyase and phenolic substances. Thin layer chromatographic separation of secondary metabolites revealed presence of alkaloid and terpenoid compounds in the leaf extracts of Z. jujuba that exhibited toxicity against R. solani under in vitro condition. Thus, the enhanced sheath blight resistance in rice seedlings treated with leaf extracts of Z. jujuba or I. carnea can be attributed to the direct inhibitory effects of these leaf extracts as well as their ability to elicit systemic resistance against R. solani

LPS-induced decrease in intracellular labile zinc, [Zn]i, contributes to apoptosis in cultured sheep pulmonary artery endothelial cells

A role in signal transduction for a vanishingly small labile pool of intracellular zinc ([Zn]i) has been inferred by the sensitivity of various physiological pathways to zinc chelators such as N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and/or associations with changes in nonprotein-bound zinc-sensitive fluorophores. Although we (44) reported that LPS-induced apoptosis in cultured sheep pulmonary artery endothelial cells (SPAEC) was exacerbated by TPEN, 1) we did not detect acute (30 min) changes in [Zn]i, and 2) it is unclear from other reports whether LPS increases or decreases [Zn]i and whether elevations or decreases in [Zn]i are associated with cell death and/or apoptosis. In the present study, we used both chemical (FluoZin-3 via live cell epifluorescence microscopy and fluorescence-activated cell sorting) and genetic (luciferase activity of a chimeric reporter encoding zinc-sensitive metal-response element and changes in steady-state mRNA of zinc importer, SLC39A14 or ZIP14) techniques to show that LPS caused a delayed time-dependent (2–4 h) decrease in [Zn]i in SPAEC. A contributory role of decreases in [Zn]i in LPS-induced apoptosis (as determined by caspase-3/7 activation, annexin-V binding, and cytochrome c release) in SPAECs was revealed by mimicking the effect of LPS with the zinc chelator, TPEN, and inhibiting LPS- (or TPEN)-induced apoptosis with exogenous zinc. Collectively, these are the first data demonstrating a signaling role for decrease in [Zn]i in pulmonary endothelial cells and suggest that endogenous levels of labile zinc may affect sensitivity of pulmonary endothelium to the important and complex proapoptotic stimulus of LPS