Hypoxia-induced mitochondrial stress granules.

Perturbations of mitochondrial proteostasis have been associated with aging, neurodegenerative diseases, and recently with hypoxic injury. While examining hypoxia-induced mitochondrial protein aggregation in C. elegans, we found that sublethal hypoxia, sodium azide, or heat shock-induced abundant ethidium bromide staining mitochondrial granules that preceded evidence of protein aggregation.

Effect of the mitochondrial unfolded protein response on hypoxic death and mitochondrial protein aggregation.

Mitochondria are the main oxygen consumers in cells and as such are the primary organelle affected by hypoxia. All hypoxia pathology presumably derives from the initial mitochondrial dysfunction. An early event in hypoxic pathology in C.

A screen for protective drugs against delayed hypoxic injury.

Despite longstanding efforts to develop cytoprotective drugs against ischemia/reperfusion (IR) injuries, there remains no effective therapeutics to treat hypoxic injury. The failure of traditional strategies at solving this problem suggests the need for novel and unbiased approaches that can lead to previously unsuspected targets and lead compounds. Towards this end, we report here a unique small molecule screen in the nematode C.

Investigation of RNA interference suppression of matrix metalloproteinase-9 in mouse model of atherosclerosis.

Objective: To investigate the effect of RNA interference of matrix metalloproteinase (MMP)-9 on atherosclerosis on atherosclerosis in apolipoprotein E (ApoE)-/- mouse.

Methods: ApoE-/- mouse strain and three cell lines (293T, NIH3T3 and Raw264.7) were used in the present study to investigate the effect of MMP-9 silencing by RNA interference.

Synthesis and Anticonvulsant Activity Evaluation of 3-alkoxy-4-(4-(hexyloxy/heptyloxy)phenyl)-4H-1,2,4 -triazole.

A series of 3-alkoxy-4-(4-(hexyloxy/heptyloxy) phenyl)-4H-1,2,4-triazole was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, compound 3-heptyloxy-4-(4-(hexyloxy) phenyl)-4H-1,2,4-triazole (5f) was the most active one and also had the lowest toxicity.

[Virus spectrum features of adult influenza-like fever in outpatients].

Objective: To analyze the results of detection on respiratory virus of influenza-like illness ( ILI ) in Beijing from June 2010 to February 2012 and understand the virus spectrum of adult influenza-like fever.

Methods: A total of 502 swabs were collected and 279 throat swabs tested for 12 respiratory viruses with multiplex reverse transcription-polymerase chain reaction (RT-PCR). And 413 swabs were tested for pH1N1 by virus isolation influenza viruses.

Role of oxygen consumption in hypoxia protection by translation factor depletion.

The reduction of protein synthesis has been associated with resistance to hypoxic cell death. Which components of the translation machinery control hypoxic sensitivity and the precise mechanism has not been systematically investigated, although a reduction in oxygen consumption has been widely assumed to be the mechanism. Using genetic reagents in Caenorhabditis elegans, we examined the effect on organismal survival after hypoxia of knockdown of 10 factors functioning at the three principal steps in translation.

Damaged DNA-binding protein 2 (DDB2) protects against UV irradiation in human cells and Drosophila.

Background: We observed previously that cisplatin-resistant HeLa cells were cross-resistant to UV light due to accumulation of DDB2, a protein implicated in DNA repair. More recently, we found that cFLIP, which represents an anti-apoptotic protein whose level is induced by DDB2, was implicated in preventing apoptosis induced by death-receptor signaling. In the present study, we investigated whether DDB2 has a protective role against UV irradiation and whether cFLIP is also involved in this process.

Role of C. elegans TAT-1 protein in maintaining plasma membrane phosphatidylserine asymmetry.

The asymmetrical distribution of phospholipids on the plasma membrane is critical for maintaining cell integrity and physiology and for regulating intracellular signaling and important cellular events such as clearance of apoptotic cells. How phospholipid asymmetry is established and maintained is not fully understood. We report that the Caenorhabditis elegans P-type adenosine triphosphatase homolog, TAT-1, is critical for maintaining cell surface asymmetry of phosphatidylserine (PS).

C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1.

Externalization of phosphatidylserine, which is normally restricted to the inner leaflet of plasma membrane, is a hallmark of mammalian apoptosis. It is not known what activates and mediates the phosphatidylserine externalization process in apoptotic cells. Here, we report the development of an annexin V-based phosphatidylserine labelling method and show that a majority of apoptotic germ cells in Caenorhabditis elegans have surface-exposed phosphatidylserine, indicating that phosphatidylserine externalization is a conserved apoptotic event in worms.

[Expression of novel apoptosis-related protein PDCD5 in granulosa cells of polysystic ovary syndrome].

Objective: To detect the novel apoptosis-related protein PDCD5 expression in granulosa cells of polysystic ovary syndrome (PCOS) and normal ovary, and explore the pathogenesis of PCOS.

Methods: The granulosa cells were collected from 30 cases of PCOS and normal ovary in IVF-ET. Expression of PDCD5 was detected by flow cytometry; immunofluorescence and immunohistochemistry.

Potential attenuation of p38 signaling by DDB2 as a factor in acquired TNF resistance.

Our previous study demonstrated that DDB2, a DNA repair protein, attenuates cell surface membrane-associated death signal induced by UV or FasAb; DDB2 is overexpressed in cisplatin-selected cells. However, the molecular mechanism underlying the protective role of DDB2 along the apoptotic pathway remains unknown. Our study identified the cross-resistance of the cisplatin-selected cells to tumor necrosis factor-alpha (TNF-alpha).

Cross-resistance to death ligand-induced apoptosis in cisplatin-selected HeLa cells associated with overexpression of DDB2 and subsequent induction of cFLIP.

This work reports the involvement of damaged DNA-binding protein 2 (DDB2), a component involved in the genomic repair of UV damage, in the cross-resistance of cisplatin-selected cell lines to death ligand-mediated apoptosis. The cisplatin-resistant cell line (HR3) exhibits enhanced expression of DDB2 and cross-resistance to UV-induced activation of apoptosis and caspases. This investigation further demonstrates that HR3 cells also exhibited cross-resistance to death ligands [Fas-inducing antibody and tumor necrosis factor (TNF)-alpha].

[The differential expression profile of polycystic ovary syndrome associated genes].

Objective: To explore the gene differential expression pattern of polycystic ovary syndrome.

Methods: We carried out microarray analysis to define the gene networks by the PCOS granulosa cells in order to identify differentially expressed genes in PCOS patients. These granulosa cells of five PCOS cases and five control cases which were derived during oocyte retrieval from women undergoing IVF.