Biomedical subjects

Xiaoling Li

Publications and source records attributed to Xiaoling Li.

49 records · Page 3Linked to original sources

PubMed2003

The dynamin-like GTPase DLP1 is essential for peroxisome division and is recruited to peroxisomes in part by PEX11.

Peroxisome division involves the conserved PEX11 peroxisomal membrane proteins and in yeast has been shown to require Vps1p, a dynamin-like protein. We show here that DLP1, the human homolog of the yeast DNM1 and VPS1 genes, plays an important role in peroxisome division in human cells. Disruption of DLP1 function by either RNA interference or overexpressing dominant negative DLP1 mutants causes a dramatic reduction in peroxisome abundance, although overexpression of functional DLP1 has no effect on peroxisome abundance. Overexpression of PEX11 induces peroxisome division in a multistep process involving elongation of preexisting peroxisomes followed by their division. We find that DLP1 is dispensable for the first phase of this process but essential for the second. Furthermore, we show that DLP1 associates with peroxisomes and that PEX11 overexpression recruits DLP1 to peroxisome membranes. However, we were unable to detect physical interaction between PEX11 and DLP1, and the stoichiometry of PEX11 and peroxisome-associated DLP1 was far less than 1:1. Based on these and other aspects, we propose that DLP1 performs an essential but transient role in peroxisome division and that PEX11 promotes peroxisome division by recruiting DLP1 to peroxisome membranes through an indirect mechanism.

Animals↗

PubMed2003

Identification of tissue-specific genes in nasopharyngeal epithelial tissue and differentially expressed genes in nasopharyngeal carcinoma by suppression subtractive hybridization and cDNA microarray.

Suppression subtractive hybridization (SSH) was performed for isolation of tissue-specific genes in nasopharyngeal epithelial tissue, by use of cDNAs from human adult nasopharyngeal epithelial tissue as tester and mixed cDNAs from esophagus, lung, liver, heart, stomach, spleen, skeletal muscle, kidney, and skin as drivers. Fourteen differentially expressed genes in nasopharyngeal epithelial tissue were obtained. Among these genes, LPLUNC1 and SPLUNC1 were confirmed to be specifically expressed in nasopharyngeal epithelial tissue and the trachea. A novel transcript of SPLUNC1, which we designate NASG, was found. We also combined SSH and cDNA microarray hybridization to identify genes whose expressions were altered in nasopharyngeal carcinoma (NPC). We used NPC cell line HNE1 and primary human embryo nasopharyngeal epithelial cells in one SSH experiment, and NPC biopsies and normal adult nasopharyngeal epithelial tissue in another. Some 1,200 SSH inserts from four subtractive cDNA libraries were arrayed onto nylon membranes by use of robotic printing. Differential gene expression was verified by hybridizing of the membranes with radioactively labeled first-strand cDNA from NPC cell line HNE1, primary human embryo nasopharyngeal epithelial cells, NPC biopsies, and normal adult nasopharyngeal epithelial tissue. Seventeen differentially expressed genes in NPC were obtained. Among these genes, we identified SPLUNC1 and LPLUNC1 to be down-expressed in NPC biopsies (34/48, 33/48).

Adult↗

PubMed2003

Regulation of heme oxygenase expression by cyclopentenone prostaglandins.

Prostaglandins (PGs) originate from the degradation of membranar arachidonic acid by cyclooxygenases (COX-1 and COX-2). The prostaglandin actions in the nervous system are multiple and have been suggested to play a significant role in neurodegenerative disorders. Some PGs have been reported to be toxic and, interestingly, the cyclopentenone PGs have been reported to be cytoprotective at low concentration and could play a significant role in neuronal plasticity. They have been shown to be protective against oxidative stress injury; however, the cellular mechanisms of protection afforded by these PGs are still unclear. It is postulated that the cascade leading to neuronal cell death in acute and chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer's disease, would be mediated by free radical damage. We tested the hypothesis that the neuroprotective action of cyclopentanone could be caused partially by an induction of heme oxygenase 1 (HO-1). We and others have previously reported that modulation of HO total activity may well have direct physiological implications in stroke and in Alzheimer's disease. HO acts as an antioxidant enzyme by degrading heme into iron, carbon monoxide, and biliverdin that is rapidly converted into bilirubin. Using mouse primary neuronal cultures, we demonstrated that PGs of the J series induce HO-1 in a dose-dependent manner (0, 0.5, 5, 10, 20, and 50 micro g/ml) and that PGJ(2) and dPGJ(2) were more potent than PGA(2), dPGA(2), PGD(2), and PGE(2). No significant effects were observed for HO-2 and actin expression. In regard to HO-3 expression found in rat, with its protein deducted sequence highly homologous to HO-2, no detection was observed in HO-2(-/-) mice, suggesting that HO-3 protein would not be present in mouse brain. We are proposing that several of the protective effects of PGJ(2) could be mediated through beneficial actions of heme degradation and its metabolites. The design of new mimetics based on the cyclopentenone structure could be very useful as neuroprotective agents and be tested in animal models of stroke and Alzheimer's disease.

Animals↗

PubMed2002

Thin films of Ag nanoparticles prepared from the reduction of AgI nanoparticles in self-assembled films.

A novel method for the preparation of thin films of Ag nanoparticles is reported. Using mercaptoacetic acid as the stabilizing agent, AgI nanoparticles were prepared in aqueous solution. And based on electrostatic interactions, the thiol-passivated AgI nanoparticles were assembled in a self-assembled film by alternative deposition with a cationic polyelectrolyte. Then the AgI nanoparticles in the composite film were reduced by NaBH(4), which resulted in the formation of a thin film of Ag nanoparticles. UV-visible spectra and X-ray photoelectron spectroscopy data confirmed the transformation from AgI to Ag. Atomic force microscopy (AFM) showed that the formed Ag nanoparticles distributed on the film homogeneously. Surface-enhanced Raman spectroscopy (SERS) measurement indicated that the prepared thin films could be used as effective SERS substrates. The reduction process was also carried out by UV light at selective surface regions, which resulted in the formation of patterned nanoparticle arrays.

Journal Article↗

PubMed2002

[The protective mechanism of fructose-1, 6-diphosphate on ischemic brain injury].

OBJECTIVE: To explore the protective mechanism of fructose-1, 6-diphosphate (FDP) on ischemic brain injury. METHODS: A model of permanent focal cerebral ischemia was performed in rats by intraluminal filament occlusion of middle cerebral artery. TTC staining, immunohistochemistry, Western blotting, and TUNEL staining were used to evaluate the effect of FDP on infarct area, apurinic/apyrimidinic endonuclease (APE/Ref-1) expression, and apoptosis in ischemic brain tissue. RESULT: The infarct areas of FDP intervening group and ischemia for 24 h group were 31.0 +/- 2.9 mm(2) and 47.3 +/- 6.0 mm(2) respectively. The numbers of TUNEL positive cells in ischemic penumbra were 69.3 +/- 2.4/mm(2) and 42.8 +/- 1.7/mm(2) in FDP group and ischemia for 24 h group respectively. FDP upregulated the expression of APE/Ref-1 protein in ischemic penumbra. The numbers of APE/Ref-1 immuno-positive cells in the ischemia for 24 h group and FDP group were 47 +/- 3.4/mm(2) and 26.3 +/- 2.9/mm(2) respectively. The values of optical density by Western blotting in these two groups were 5.3 +/- 3.2 and 13.8 +/- 5.4 respectively. The differences between these two groups were statistically significant. CONCLUSION: Through upregulating the expression of APE/Ref-1 protein, FDP improves the repair ability of brain tissue in the course of ischemic injury and mitigated the quantity of apoptosis in penumbra, thus preventing the extension of cerebral infarction.

Animals↗

PubMed2002

PEX11 promotes peroxisome division independently of peroxisome metabolism.

The PEX11 peroxisomal membrane proteins are the only factors known to promote peroxisome division in multiple species. It has been proposed that PEX11 proteins have a direct role in peroxisomal fatty acid oxidation, and that they only affect peroxisome abundance indirectly. Here we show that PEX11 proteins are unique in their ability to promote peroxisome division, and that PEX11 overexpression promotes peroxisome division in the absence of peroxisomal metabolic activity. We also observed that mouse cells lacking PEX11beta display reduced peroxisome abundance, even in the absence of peroxisomal metabolic substrates, and that PEX11beta(-/-) mice are partially deficient in two distinct peroxisomal metabolic pathways, ether lipid synthesis and very long chain fatty acid oxidation. Based on these and other observations, we propose that PEX11 proteins act directly in peroxisome division, and that their loss has indirect effects on peroxisome metabolism.

Animals↗

PubMed2002

Transbuccal delivery of 2',3'-dideoxycytidine: in vitro permeation study and histological investigation.

Permeation of 2',3'-dideoxycytidine (ddC), an ionic compound, through buccal mucosa was investigated in this in vitro study to identify the major permeation barrier within the epithelium of buccal mucosa and explore the feasibility of transbuccal delivery of ddC. In vitro permeation of ddC across porcine buccal mucosa was conducted in isotonic McIlvaine buffer solution (IMB) using in-line flow through diffusion cells at 37 degrees C. Sodium glycodeoxycholate (GDC) was used as the permeation enhancer in the permeation enhancement studies. Light microscopy was used in the histological studies of buccal tissue. The steady-state flux of ddC permeating through buccal mucosa increased linearly (R(2)=0.96, P<0.05) as the donor concentration of ddC was increased from 1 to 20 mg/ml. The permeabilities for the full thickness buccal mucosa, the epithelium, and the connective tissue were determined to be 1.75+/-0.74x10(-7), 2.90+/-1.86x10(-7), and 3.49+/-1.19x10(-6) cm/s, respectively. The permeability of ddC was significantly (P<0.05) enhanced by GDC at a concentration of 4 mM. The histological study revealed that the thickness of epithelium was greatly reduced after buccal tissues were immersed in IMB for 12 and 24 h but the basal lamina remained intact even after 24 h. A bilayer diffusion model was established to quantitatively describe the contributions of the epithelium and the connective tissue to the permeation barrier. In conclusion, ddC permeated through buccal mucosa by passive diffusion over the range of concentrations examined. The basal lamina layer within the epithelium of buccal mucosa acted as an important barrier to the permeation of ddC. GDC effectively enhanced the buccal permeability of ddC. The transbuccal delivery is a potential route for the administration of ddC.

Administration, Buccal↗

PubMed2002

PEX11 beta deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function.

Zellweger syndrome is a lethal neurological disorder characterized by severe defects in peroxisomal protein import. The resulting defects in peroxisome metabolism and the accumulation of peroxisomal substrates are thought to cause the other Zellweger syndrome phenotypes, including neuronal migration defects, hypotonia, a developmental delay, and neonatal lethality. These phenotypes are also manifested in mouse models of Zellweger syndrome generated by disruption of the PEX5 or PEX2 gene. Here we show that mice lacking peroxisomal membrane protein PEX11 beta display several pathologic features shared by these mouse models of Zellweger syndrome, including neuronal migration defects, enhanced neuronal apoptosis, a developmental delay, hypotonia, and neonatal lethality. However, PEX11 beta deficiency differs significantly from Zellweger syndrome and Zellweger syndrome mice in that it is not characterized by a detectable defect in peroxisomal protein import and displays only mild defects in peroxisomal fatty acid beta-oxidation and peroxisomal ether lipid biosynthesis. These results demonstrate that the neurological pathologic features of Zellweger syndrome can occur without peroxisomal enzyme mislocalization and challenge current models of Zellweger syndrome pathogenesis.

Animals↗

PubMed2002

PEX11alpha is required for peroxisome proliferation in response to 4-phenylbutyrate but is dispensable for peroxisome proliferator-activated receptor alpha-mediated peroxisome proliferation.

The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes. As part of our effort to understand the molecular and physiological functions of PEX11 proteins, we disrupted the mouse PEX11alpha gene. Overexpression of PEX11alpha is sufficient to promote peroxisome division, and a class of chemicals known as peroxisome proliferating agents (PPAs) induce the expression of PEX11alpha and promote peroxisome division. These observations led to the hypothesis that PPAs induce peroxisome abundance by enhancing PEX11alpha expression. The phenotypes of PEX11alpha(-/-) mice indicate that this hypothesis remains valid for a novel class of PPAs that act independently of peroxisome proliferator-activated receptor alpha (PPARalpha) but is not valid for the classical PPAs that act as activators of PPARalpha. Furthermore, we find that PEX11alpha(-/-) mice have normal peroxisome abundance and that cells lacking both PEX11alpha and PEX11beta, a second mammalian PEX11 gene, have no greater defect in peroxisome abundance than do cells lacking only PEX11beta. Finally, we report the identification of a third mammalian PEX11 gene, PEX11gamma, and show that it too encodes a peroxisomal protein.

Amino Acid Sequence↗

PubMed2002

Early appearance of functional deficits after neonatal excitotoxic and hypoxic-ischemic injury: fragile recovery after development and role of the NMDA receptor.

We sought to determine whether neonatal rats that sustain unilateral cerebral hypoxic-ischemic or excitotoxic insults (1) manifest contralateral sensorimotor deficits during development or in adulthood and (2) recover from those deficits. Seven-day-old (P7) rats received a right intrastriatal injection of the glutamate analog N-methyl-D-aspartate (NMDA). Unilateral hypoxia-ischemia (HI) was induced by right carotid ligation followed by 1.5 h in 8% O2. Both procedures produce neuronal loss in the striatum and sensorimotor cortex. Nonlesioned controls were included. We scored percent forepaw placement on the edge of a horizontal surface, with lateral vibrissa stimulation, from P9 to P19, and at P33 and P50. Then, on P50, rats were treated with the NMDA antagonist MK-801 to determine whether deficits could be reinstated. NMDA- and HI-lesioned rats exhibited a deficit in contralateral vibrissa-stimulated forepaw placing that emerged during the second week of life. Yet, by P33 and P50, the lesioned groups and controls were indistinguishable. MK-801 injection on P50 resulted in transient reinstatement of the placing deficit. After unilateral neonatal excitotoxic or HI brain injury, contralateral sensorimotor deficits are detected, but in many animals, these deficits have resolved by adulthood. Thus, timing of sensorimotor tests may influence their sensitivity for detection of focal neuropathology originating in the neonatal period.

Animals↗

PubMed2002

Dihydrotestosterone inhibits granulosa cell proliferation by decreasing the cyclin D2 mRNA expression and cell cycle arrest at G1 phase.

Hyperandrogenism is known to perturb ovarian physiology resulting in anovulatory conditions. In the ovary, androgens produced by theca-interstitial cells are converted to estrogens in granulosa cells under the influence of FSH and LH. In some of the target organs, including the ovary, androgens are also converted into their 5alpha reduced metabolites. In the present study, we examined the molecular mechanism by which dihydrotestosterone (DHT), a 5alpha reduced metabolite of testosterone, mediates the inhibition of granulosa cell proliferation, using a rat model. Immature female rats were primed with estradiol, followed by DHT administration for 2 d and granulosa cells were cultured in the presence or absence of forskolin. Granulosa cells from the DHT-treated rats showed reduced [(3)H]thymidine incorporation into DNA and reduced cell number in response to forskolin stimulation, compared with control. The decreased responsiveness of DHT-treated granulosa cells to forskolin was not due to increased apoptosis because the expression of cleaved caspase 3 remained the same in both control and DHT-exposed granulosa cells stimulated with forskolin. Forskolin treatment stimulated the expression of cyclin D2 mRNA in control granulosa cells, whereas DHT treatment abolished this response. In vitro DHT treatment of granulosa cells for 48 h resulted in a cell cycle arrest with 70% of cells at G1 phase and 26% at S phase, and control cells exhibited a distribution of 42% and 55% at G1 and S phase, respectively. In conclusion, the present study shows that DHT inhibits the granulosa cell proliferation through a decrease in cyclin D2 mRNA expression, which leads to cell cycle arrest at the G1 phase.

Animals↗

PubMed2002

[Characteristics of optical coherence tomography for exudative age-related macular degeneration].

OBJECTIVE: To observe the characteristics of optical coherence tomography (OCT) for exudative age-related macular degeneration (AMD). METHODS: Thirty-eight patients (42 eyes) diagnosed as exudative AMD by color fundus photography, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were examined by OCT. The results of OCT were analyzed and compared with that of FFA and ICGA. RESULTS: The characteristics of OCT for exudative AMD: fibrotic choroidal neovascularization (34 eyes), serous detachment of neurosensory epithelium (38 eyes), detachment of the nerve fiber layer (8 eyes), and hemorrhagic and serous detachment of retinal pigment epithelium (11 eyes and 9 eyes, respectively). CONCLUSION: The major characteristic of OCT of exudative AMD is fibrotic choroidal neovascularization combined with serous and hemorrhagic detachment of neurosensory epithelium or retinal pigment epithelium, which would be helpful for diagnosing and evaluating exudative AMD.

Aged↗

PubMed2002

[Distribution of noniodized salt and related affecting factors in Xinjiang].

OBJECTIVE: To find out the distribution of noniodized salt and related affecting factors in Xinjiang. METHOD: Using NTTST's iodized salt inspection Plan. RESULTS: A total number of 17 973 house holds being surveyed in which 69.4% of those used iodized salt and 30.5% used noniodizd salt. In northern Xinjiang, 7 672 households being surveyed in which 83.9% used iodized salt while in eastern Xinjiang 1 200 house holds being surveyed in which 62.2% used iodized salt. In southern Xinjiang, 9 101 house holds being surveyed in which 58.2% used iodized salt. Data showed a statistically significant difference (chi(2) = 1 329.87, P < 0.01). The noniodized salt comes from shop-on-wheels (57.4%) and rock salt (23.0%). The source of iodine was different in different areas. In eastern and southern Xinjiang it came from shop-on-wheels, while in northern Xinjiang came from retail sites. Factors related to the use of iodized salt were awareness about iodine deficiency disorders (IDD) and income. CONCLUSION: Programs on fighting against iodine deficiency in Xinjiang needs more attention, especially in the following aspects as publicity on IDD, administration of salt market and supervision system.

China↗