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Biomedical subjects

Pin Lu

Publications and source records attributed to Pin Lu.

7 recordsLinked to original sources
PubMed2006

Peroxisome proliferator-activated receptor gamma promotes lymphocyte survival through its actions on cellular metabolic activities.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a metabolic regulator that plays an important role in sensitizing tissues to the action of insulin and in normalizing serum glucose and free fatty acids in type 2 diabetic patients. The receptor has also been implicated in the modulation of inflammatory responses, and ligands of PPARgamma have been found to induce apoptosis in lymphocytes. However, apoptosis induction may not depend on the receptor, because high doses of PPARgamma agonists are required for this process. Using cells containing or lacking PPARgamma, we reported previously that PPARgamma attenuates apoptosis induced by cytokine withdrawal in a murine lymphocytic cell line via a receptor-dependent mechanism. PPARgamma exerts this effect by enhancing the ability of cells to maintain their mitochondrial membrane potential during cytokine deprivation. In this report, we demonstrate that activation of PPARgamma also protects cells from serum starvation-induced apoptosis in human T lymphoma cell lines. Furthermore, we show that the survival effect of PPARgamma is mediated through its actions on cellular metabolic activities. In cytokine-deprived cells, PPARgamma attenuates the decline in ATP level and suppresses accumulation of reactive oxygen species (ROS). Moreover, PPARgamma regulates ROS through its coordinated transcriptional control of proteins and enzymes involved in ROS scavenging, including uncoupling protein 2, catalase, and copper zinc superoxide dismutase. Our studies identify cell survival promotion as a novel activity of PPARgamma and suggest that PPARgamma may modulate cytokine withdrawal-induced activated T cell death.

Animals↗
PubMed2005

ERK1 activation is required for S-phase onset and cell cycle progression after fertilization in sea urchin embryos.

Fertilization of sea urchin eggs results in a large, transient increase in intracellular free Ca2+ concentration that is responsible for re-initiation of the cell division cycle. We show that activation of ERK1, a Ca2+-dependent MAP kinase response, is required for both DNA synthesis and cell cycle progression after fertilization. We combine experiments on populations of cells with analysis at the single cell level, and develop a proxy assay for DNA synthesis in single embryos, using GFP-PCNA. We compare the effects of low molecular weight inhibitors with a recombinant approach targeting the same signalling pathway. We find that inhibition of the ERK pathway at fertilization using either recombinant ERK phosphatase or U0126, a MEK inhibitor, prevents accumulation of GFP-PCNA in the zygote nucleus and that U0126 prevents incorporation of [3H]-thymidine into DNA. Abrogation of the ERK1 signalling pathway also prevents chromatin decondensation of the sperm chromatin after pronuclear fusion, nuclear envelope breakdown and formation of a bipolar spindle.

Animals↗
PubMed2005

GFP-PCNA as an S-phase marker in embryos during the first and subsequent cell cycles.

BACKGROUND INFORMATION: Proliferating cell nuclear antigen (PCNA) is a key component of the DNA replication machinery involved in the process of DNA elongation, recombination, methylation and repair. We have used PCNA fused with green fluorescent protein (GFP-PCNA) as a convenient tool to show the progress of S-phase in single embryos in vivo. Here we make a comparison between Hoechst 33342 and GFP-PCNA as in vivo event markers for DNA synthesis. Hoechst 33342 and DAPI (4,6-diamidino-2-phenylindole) have been used as a simple and rapid method for assessing membrane permeability and staining DNA in mammalian cells. However, it is difficult to use these dyes in living embryos during cell cycle progression studies over long periods of time as they are phototoxic. Moreover, though Hoechst staining reveals nuclear morphology, it gives no information about the progress of S-phase. RESULTS: We have microinjected or expressed a GFP-PCNA chimera to develop a method which enables visualization of S-phase in sea urchin and Caenorhabditis elegans embryos during the first and subsequent embryonic cell cycles and in Drosophila stage 4 embryos during syncytial nuclear divisions. We find that nuclear accumulation of GFP-PCNA correlates with S-phase onset. Loss of the chimera from the nucleus occurs when the nuclear envelope breaks down at mitosis. CONCLUSIONS: GFP-PCNA is a accurate and non-toxic marker of S-phase in embryos during early development.

Animals↗
PubMed2004

Influence of interchannel spacing on the dynamical properties of multichannel quartz crystal microbalance.

For a multichannel quartz crystal microbalance (MQCM) device, the key problem in design is to minimize the frequency interference between adjacent channels. In this paper, the effects of interchannel separation on the resonance frequencies and frequency interference of the device are studied. The results show that, for the channels with the same size, the resonant modes will appear alternatively, and the frequency interference keeps oscillating in a very small scope in the cases of large interchannel separations. Based on the studies, the considerations for MQCM design also are discussed.

Letter↗
PubMed2003

A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice.

OBJECTIVE: The transcription of several cytokines, cell adhesion molecules, and enzymes involved in the inflammatory and destructive mechanisms of rheumatoid arthritis is dependent on nuclear factor kappa B (NF-kappa B). Because I kappa B kinase (IKK) is critical in transducing the signal-inducible activation of NF-kappa B, we examined whether the highly selective and orally bioavailable IKK inhibitor BMS-345541 is efficacious against collagen-induced arthritis (CIA) in mice. METHODS: Arthritis in DBA/1LacJ male mice was induced by subcutaneous immunization with bovine type II collagen on day 0 and day 21. BMS-345541 was administered perorally daily, either prophylactically (before disease onset) or therapeutically (after disease onset). Clinical assessment of the incidence and severity of disease was conducted throughout the study, and histologic evaluation was performed at the time of study termination (day 42). RESULTS: When administered prophylactically, BMS-345541 (in a dose range of 10-100 mg/kg) was effective, in a dose-dependent manner, in reducing the incidence of disease and inhibiting clinical signs of disease. Histologic evaluation of the joints showed that both inflammation and joint destruction were blocked by the IKK inhibitor. Message levels of interleukin-1 beta in the joints were also dose-dependently inhibited in the mice that received BMS-345541. Dose-dependent efficacy in terms of both disease severity and histologic end points was observed with the therapeutic dosing regimen of BMS-345541, with use of the 100-mg/kg dose resulting in resolution of disease. CONCLUSION: IKK plays a key role in CIA in mice, and inhibitors of this enzyme represent a promising target for the development of novel agents to treat rheumatoid arthritis and other inflammatory diseases. BMS-345541 represents the first example of an inhibitor of IKK that has antiinflammatory activity in vivo.

Administration, Oral↗
PubMed2003

Frequency interference between two mesa-shaped quartz crystal microbalances.

The multichannel quartz crystal microbalance (MQCM) is very attractive for biosensor applications. The principle of the MQCM design involves fabricating arrays of quartz microbalances on a single substrate, and it is important that the individual sensor performance is not influenced by the neighboring devices. Feasible ways to control the coupling of acoustical energy within a MQCM structure are to increase the difference in the resonance frequency between the electroded and unelectroded portions of the substrate; and a practical way to achieve this is to use mesa structures. In this paper, the frequency interference between two mesa-shaped quartz crystal microbalances is investigated using Mindlin's theory. The results show that even a very small mesa height (approximately 5% of the plate thickness) can greatly reduce the frequency interference and more effectively trap the acoustic energy. This allows for a broader design window and higher packing density for MQCM applications.

Biosensing Techniques↗