Biomedical subjects

Yin Liu

Publications and source records attributed to Yin Liu.

61 records · Page 4Linked to original sources

PubMed2003

[Molecular mechanism of metastasis inhibition of nasopharyngeal carcinoma cell CNE-2L2 induced by reduction of 6A8 alpha-mannosidase expression].

OBJECTIVE: To study the effect of inhibition of 6A8 alpha-mannosidase expression on adhesiveness among and E-cadherin expression on CNE-2L2 cells, and on metastasis of the tumors from the cells inoculated in nude mice. METHODS: Anchorage-independent adhesion among cells was examined in soft agar culture. E-cadherin expression was studied by immunofluorescence staining, immunohistological staining and RT-PCR. CNE-2L2 cells were subcutaneously inoculated into nude mice. Eight weeks later tumor metastasis was demonstrated by means of histological examination of lung sections. RESULTS: CNE-2L2 cells with suppression of 6A8 alpha-mannosidase expression (AS) became aggregated. E-cadherin expression on wild type cells was very weak. In contrast, it was greatly enhanced on AS cells. The enhancement was detected on both protein and mRNA levels. Lung metastasis of the tumor from inoculated AS cells were heavily inhibited in nude mice. CONCLUSION: Inhibition of 6A8 alpha-mannosidase expression results in enhancement of cell-cell adhesion and of E-cadherin expression on CNE-2L2 cells. Lung metastasis of the tumor grown from AS cell inoculate in nude mice is heavily suppressed.

Animals↗

PubMed2002

Calcium/calmodulin-modulated chloride and taurine conductances in cultured rat astrocytes.

Osmotically swollen rat cerebral astrocytes develop an increased anion conductance which can mediate chloride and taurine release. We used whole cell patch clamp to study mechanisms that modulate this conductance. Astrocyte chloride conductance increased within 4 min of exposure to 200 mOsm medium and was 670+/-123% of its initial value after 15 min (mean+/-S.E.M.). This conductance was substantially reduced in 0.1 mM extracellular calcium with 20 mM BAPTA added to the electrode solution and was completely inhibited with calcium-free perfusion solution containing 1 mM EDTA (n=4). The conductance increase in 200 mOsm medium also was inhibited in a dose-dependent manner by nimodipine with a calculated K(i) of 0.31+/-0.4 microM and mean+/-S.E.M. inhibition of 84.4+/-4% at 100 microM nimodipine. In the presence of 100 microM W-7, a calmodulin antagonist, the mean+/-S.E.M. conductance increase after 15 min was 223+/-40% of the initial value while 300 microM W-7 or 100 microM trifluoperazine inhibited the conductance increase completely (n=6). With taurine as the major anion in electrode and perfusion solutions, a significant conductance increase was observed in 200 mOsm medium. This conductance increase was inhibited by 300 microM W-7 or 100 microM nimodipine. We conclude extracellular calcium influx via L-type calcium channels leads to increased astrocyte anion conductance in 200 mOsm conditions via calmodulin-dependent activation of anion channels. Efflux of anionic taurine from swollen astrocytes also may be affected by calcium influx through a similar calcium/calmodulin-dependent process.

Animals↗

PubMed2002

Phosphorylation of the protein kinase C-theta activation loop and hydrophobic motif regulates its kinase activity, but only activation loop phosphorylation is critical to in vivo nuclear-factor-kappaB induction.

Protein kinase C (PKC)-theta, a member of the 'novel' subfamily of PKC isoforms, is of singular importance in transducing signals in T-lymphocytes. Since understanding of regulatory phosphorylation of novel PKCs is fragmentary and inconsistent with findings for 'classical' PKC isoforms, we investigated three potential phosphorylation sites on PKC-theta; in the activation loop (Thr(538)), turn motif (Ser(676)) and hydrophobic motif (Ser(695)). Combined evidence from phospho-specific antisera and MS demonstrates phosphorylation at all three sites. Unlike its closest paralogue, PKC-delta, lack of negative charge in the activation loop of PKC-theta results in a profound catalytic defect (>100-fold reduction in the T538A mutant); the high sequence similarity between PKC-theta and -delta assists in the formulation of structural hypotheses to account for this major difference. In contrast with mechanisms proposed for other PKC isoforms, phosphorylation at the other two sites does not reconstitute catalytic activity. Activation loop phosphorylation is critical in vivo, since the T538A mutant completely lost its capacity to mediate T-cell receptor-stimulation of nuclear factor kappaB (NF-kappaB) activation in Jurkat T-cells. Hydrophobic motif phosphorylation also substantially influences PKC-theta catalytic activity (5-fold reduction in the S695A mutant), but does not impair NF-kappaB activation in Jurkat T-cells. Its mechanism is independent of secondary effects on activation loop phosphorylation and cannot be explained by thermal instability. Turn motif phosphorylation has a limited effect on kinase activity, but negatively regulates other aspects of PKC-theta function, since the S676A mutant is more efficient than wild-type in inducing NF-kappaB activation in Jurkat T-cells. These findings expand our understanding of the roles of phosphorylation in novel PKCs, and indicate that PKC-theta is a constitutively competent kinase as a consequence of constitutive phosphorylation of its activation loop.

Amino Acid Motifs↗

PubMed2002

The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain.

As the common signal transducer for IL-6 family cytokines, gp 130 interacts with various signal molecules. Our previous work found the amino-terminal enhancer of split (AES) molecule interacts with gp130 intracellular region through its conserved glutamine-rich (Q) domain. The Q domain in AES shares high homology with those in the transcription co-repressor transducin-like enhancer of split (TLE) proteins. The yeast two-hybrid assay, gluthione S-transferase fusion protein pull-down assay and immuno-co-precipitation assay indicated that the Q domain of TLE1 is capable of binding gp130 intracellular domain, and the intracellular membrane proximal region of gp 130 containing conserved Box1 and Box2 motifs seemed essential for this interaction. The interaction between gp130 and TLE1 indicated that molecules of TLE family might play a role in gp 130 signaling.

Antigens, CD↗

PubMed2002

Inhibition of 6A8 alpha-mannosidase causes oncosis-like death of BJAB cells.

To study relationships between glycosylation and cell survival we used a human alpha-mannosidase, 6A8, recently discovered in our laboratory. We found that glycosylation of BJAB cells was modified when cells were transduced with a fragment of antisense 6A8 cDNA, which resulted in an inhibition of 6A8 alpha-mannosidase expression. In comparison to wild type, mock- or sense 6A8-tansduced cells, the antisense 6A8-transduced cells showed increased cell death in culture. The dying cells were characterized by cell and nucleus swelling, membrane blebbing, organelle dilation and membrane breaking at the blebbing sites. They did not have apoptotic bodies. Annexin-V staining and DNA fragmentation assays also showed no evidence of apoptosis in these cells. This data implied that BJAB cells underwent an oncosis-like cell death upon transduction with a fragment of antisense 6A8 cDNA, which inhibited 6A8 alpha-mannosidase expression and therefore modified glycosylation of proteins shown by Con A binding test. These data imply that 6A8 alpha-mannosidase plays an important role in preventing oncosis-like death in BJAB cells. The possible mechanism of cell death by oncosis was discussed.

Cell Death↗

PubMedDate not supplied

Clobetasol propionate shampoo 0.05%: a new option to treat patients with moderate to severe scalp psoriasis.

Psoriasis is a chronic, papulosquamous condition that affects up to 2% of the U.S. population. Approximately 50% of patients with psoriasis have involvement of the scalp. This was a multicentre, randomized, vehicle-controlled, double-masked and parallel-group study. The aim was to evaluate the efficacy and safety of clobetasol propionate shampoo, 0.05% versus its corresponding vehicle in subjects aged 12 years and older with moderate to severe scalp psoriasis over a treatment period of 4 weeks. Recurrence of scalp psoriasis was assessed during a two week follow-up period. A total of 142 subjects were treated. Results after 4 weeks demonstrated that clobetasol propionate shampoo, 0.05% was with a similar safety profile significantly more effective than its vehicle. The novel short contact shampoo formulation of clobetasol propionate is convenient and efficacious and minimizes systemic exposure while being efficient, safe and well-tolerated in the treatment of moderate to severe scalp psoriasis.

Administration, Topical↗

PubMedDate not supplied

Clobetasol propionate 0.05% lotion in the treatment of moderate to severe atopic dermatitis: a randomized evaluation versus clobetasol propionate emollient cream.

Atopic dermatitis (AD) is a chronic inflammatory and pruritic skin disorder marked by alternating periods of relapse and remission. This multicenter, randomized, active- and vehicle-controlled, investigator-blinded study compared the efficacy and safety of clobetasol propionate lotion to clobetasol propionate cream formulation and lotion vehicle in the treatment of moderate to severe AD. A total of 229 subjects applied treatment twice-daily for 2 weeks. Clobetasol propionate lotion was significantly more effective than its lotion vehicle at 2 weeks and comparable to the cream formulation. Clinical success after a 2-week, treatment-free follow-up period was greater in the clobetasol propionate lotion group than in the cream group. Clobetasol propionate lotion is effective, safe, well tolerated and offers a better remission profile in the treatment of moderate to severe AD as compared to clobetasol propionate emollient cream.

Administration, Topical↗