Interaction between endoplasmic reticulum stress and caspase 8 activation in retrovirus MoMuLV-ts1-infected astrocytes

AbstractThe murine retrovirus, MoMuLV-ts1, induces progressive paralysis and immune deficiency in FVB/N mice. We have reported previously that ts1 infection causes apoptosis in astrocytes via endoplasmic reticulum (ER) and mitochondrial stress (Liu, N., Kuang, X., Kim, H.T., Stoica, G., Qiang, W., Scofield, V.L., Wong, P.K.Y. Wong. 2004. Possible involvement of both endoplasmic reticulum- and mitochondria-dependent pathways in MoMuLV-ts1-induced apoptosis in astrocytes. J. NeuroVirol. 10, 189–198). In the present study, we show that caspase 8 activation in these cells is mediated through ER stress-associated elevation of death receptor DR5 and the C/EBP homologous protein (GADD153/CHOP), an ER stress-initiated transcription factor, rather than through TNFα and TNF-R1 interactions on the cell surface. Treatment with Z-IETD-FMK, a specific inhibitor of caspase 8 enzymatic activity, reduced ER stress by two mechanisms: by inhibiting caspase 8 activation, and by preventing cleavage of the ER-associated membrane protein BAP31 into BAP20, which exacerbates the ER stress response. These findings suggest that caspase 8- and ER stress-associated apoptotic pathways are linked in ts1-infected astrocytes

Constituents leached by tomato seeds regulate the behavior of root-knot nematodes and their antifungal effects against seed-borne fungi

Germinating seeds can release diverse phytochemicals that repel, inhibit, or kill pathogens such as root-knot nematodes and seed-borne fungi. However, little is known about the composition of these phytochemicals and their effects on pathogens. In this study, we demonstrated that tomato seed exudates can attract the nematode Meloidogyne incognita using a dual-choice assay. Eighteen compounds were then isolated and identified from the exudates. Of these, esters (1-3), fatty acids (4-6), and phenolic acids (10-12) were proven to be the signaling molecules that facilitated the host-seeking process of second-stage juveniles (J2s) of nematodes, while alkaloids (17 and 18) disrupted J2s in locating their host. Furthermore, some phenolic acids and alkaloids showed antifungal effects against seed-borne fungi. In particular, ferulic acid (12) showed obvious activity against Aspergillus flavus (minimum inhibitory concentration (MIC), 32 μg/mL), while dihydrocapsaicin (17) showed noticeable activity against Fusarium oxysporum (MIC, 16 μg/mL). Overall, this study presents the first evidence that M. incognita can be attracted to or deterred by various compounds in seed exudates through identification of the structures of the compounds in the exudates and analysis of their effects on nematodes. Furthermore, some antifungal compounds were also found. The findings of this work suggest that seed exudates are new source for finding insights into the development of plant protective substances with nematocidal and antifungal effects

Improvement of Photocatalytic Performance for the g-C3N4/MoS2 Composite Used for Hypophosphite Oxidation

The synthesized g-C3N4/MoS2 composite was a high-efficiency photocatalytic for hypophosphite oxidation. In this work, a stable and cheap g-C3N4 worked as the chelating agent and combined with the MoS2 materials. The structures of the fabricated g-C3N4/MoS2 photocatalyst were characterized by some methods including X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectra (XPS). Moreover, the photocatalytic performances of various photocatalysts were measured by analyzing the oxidation efficiency of hypophosphite under visible light irradiation and the oxidation efficiency of hypophosphite using the g-C3N4/MoS2 photocatalyst which was 93.45%. According to the results, the g-C3N4/MoS2 composite showed a promising photocatalytic performance for hypophosphite oxidation. The improved photocatalytic performance for hypophosphite oxidation was due to the effective charge separation analyzed by the photoluminescence (PL) emission spectra. The transient photocurrent response measurement indicated that the g-C3N4/MoS2 composites (2.5 μA cm–2) were 10 times improved photocurrent intensity and 2 times improved photocurrent intensity comparing with the pure g-C3N4 (0.25 μA cm–2) and MoS2 (1.25 μA cm–2), respectively. The photocatalytic mechanism of hypophosphite oxidation was analyzed by adding some scavengers, and the recycle experiments indicated that the g-C3N4/MoS2 composite had a good stability

Activation of Transcription Factor Nrf-2 and Its Downstream Targets in Response to Moloney Murine Leukemia Virus ts1-Induced Thiol Depletion and Oxidative Stress in Astrocytes

The neuroimmunodegenerative syndrome that develops in mice infected with ts1, a mutant of Moloney murine leukemia virus, resembles human AIDS. Both ts1 and human immunodeficiency virus type 1 infect astrocytes, microglia, and oligodendrocytes but do not infect neurons. Oxidative stress has been implicated in the neuropathology of AIDS dementia and other neurodegenerative diseases. We report here that ts1 infection of astrocytes (both transformed C1 cells and primary cultures) also induces thiol (i.e., glutathione and cysteine) depletion and reactive oxygen species (ROS) accumulation, events occurring in parallel with viral envelope precursor gPr80(env) accumulation and upregulated expression of endoplasmic reticulum chaperones GRP78 and GRP94. Furthermore, ts1-infected astrocytes mobilize their thiol redox defenses by upregulating levels of the Nrf-2 transcription factor, as well its targets, the xCT cystine/glutamate antiporter, γ-glutamylcysteine ligase, and glutathione peroxidase. Depleting intracellular thiols by treating uninfected astrocytes with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, or by culturing in cystine-deficient medium, also induces ROS accumulation, activates Nrf-2, and upregulates Nrf-2 target gene expression in these astrocytes. Overexpression of Nrf-2 in astrocytes specifically increases expression of the above thiol synthesis-related proteins. Further treatment with BSO or N-acetylcysteine in transfected cells modulates this expression. Thiol depletion also accelerates cell death, while thiol supplementation promotes survival of ts1-infected cells. Together, our results indicate that ts1 infection of astrocytes, along with ts1-induced gPr80(env) accumulation, endoplasmic reticulum stress, thiol depletion, and oxidative stress, accelerates cell death; in response to the thiol depletion and oxidative stress, astrocytes activate their Nrf-2-mediated thiol antioxidant defenses, promoting cell survival