Biomedical subjects

Lin Zeng

Publications and source records attributed to Lin Zeng.

12 recordsLinked to original sources

PubMed2026

Comprehensive multi-post-translational modifications profiling reveals age-associated remodeling in skeletal muscle.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a major hallmark of aging. Post-translational modifications (PTMs) play essential roles in regulating protein activity and cellular homeostasis; however, how multiple PTMs are remodeled during skeletal muscle aging remains incompletely characterized. Here, we performed comprehensive multi-layered proteomic profiling of skeletal muscle from young (3-month-old) and aged (24-month-old) mice, systematically quantifying the global proteome together with five major PTMs: acetylation, phosphorylation, N-glycosylation, O-glycosylation, and ubiquitination. In total, we identified 5 337 proteins and mapped thousands of PTM sites, generating an integrated atlas of age-associated proteomic and PTM remodeling in skeletal muscle. Pathway enrichment analyses revealed distinct modification-specific patterns: acetylation and phosphorylation were predominantly associated with metabolic and mitochondrial-related pathways; N-glycosylation was enriched in immune- and secretory pathway-related processes; O-glycosylation was associated with muscle contraction-related pathways; and ubiquitination was preferentially linked to cytoskeletal organization in muscle cells. Correlation analyses further uncovered diverse association patterns among different PTMs across protein- and modification-level datasets. Phosphorylation and ubiquitination exhibited consistent positive associations, whereas acetylation and ubiquitination showed both inverse and concordant co-variation patterns across subsets of proteins. Phosphorylation and O-glycosylation displayed heterogeneous association patterns across different proteins, and acetylation and phosphorylation demonstrated positive correlations with distinct age-associated directional changes across protein subsets. Together, these results provide a comprehensive, multi-dimensional view of age-associated remodeling of the skeletal muscle proteome and multiple PTM layers, offering a valuable resource for understanding molecular alterations accompanying muscle aging and sarcopenia.

Animals↗

PubMed2006

TBLR1 regulates the expression of nuclear hormone receptor co-repressors.

BACKGROUND: Transcription is regulated by a complex interaction of activators and repressors. The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes. RESULTS: TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone transcription factors. A single highly conserved gene encodes a small family of protein molecules. Different isoforms are produced by differential exon utilization. Although the ORF of the predominant form contains only 1545 bp, the human gene occupies approximately 200 kb of genomic DNA on chromosome 3q and contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank: NM030921] locus. The murine homologue is structurally similar and is also located on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level) to TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form of TBLR1 has been demonstrated in human material and it too has an unique pattern of expression. TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. In resting cells TBLR1 is primarily cytoplasmic but after perturbation the protein translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C-terminal deletion variants, have elevated levels of endogenous N-CoR. Co-transfection of TBLR1 and SMRT results in increased expression of SMRT. This co-repressor undergoes ubiquitin-mediated degradation and we suggest that the stabilization of the co-repressors by TBLR1 occurs because of a novel mechanism that protects them from degradation. Transient over expression of TBLR1 produces growth arrest. CONCLUSION: TBLR1 is a multifunctional co-repressor of transcription. The structure of this family of molecules is highly conserved and closely related co-repressors have been found in all eukaryotic organisms. Regulation of co-repressor expression and the consequent alterations in transcriptional silencing play an important role in the regulation of differentiation.

Amino Acid Sequence↗

PubMed2006

A novel signal transduction system and feedback loop regulate fructan hydrolase gene expression in Streptococcus mutans.

The fruA gene of Streptococcus mutans encodes for a secreted fructan hydrolase (fructanase), an established virulence determinant required for releasing D-fructose from levan- and inulin-type fructans. Expression of fruA is under the control of carbon catabolite repression and is induced by growth in fructans. In this report, we identified an operon in S. mutans UA159 encoding a two-component system flanked by two predicted carbohydrate-binding proteins that is absolutely required for the expression of fruA. All four genes were found to be required for optimal growth of S. mutans on inulin-containing medium and for transcriptional activation of fruA. Complementation assays using a plasmid expressing the response regulator suggested that the two-component system works in concert with the sugar-binding proteins. This operon was also shown to activate a four-gene cluster located immediately downstream and encoding an Enzyme II (EII(Lev)) for a fructose/mannose sugar : phosphotransferase enzyme, which was found to negatively regulate the expression of fruA. Using transcriptional fusions, it was found that fructose could signal induction of the fruA and levD operons through the two-component system/sugar-binding protein complex. A recombinant LevR protein was shown to bind to the promoter regions of fruA and levD in gel mobility shift assays. Thus, a 'four-component signal transduction system' activates fructan catabolism and the expression of an Enzyme II complex that functions in a feedback loop to sense the accumulation of the end-product of fructan degradation.

Bacterial Proteins↗

PubMed2006

Characterization of cis-acting sites controlling arginine deiminase gene expression in Streptococcus gordonii.

The arginine deiminase system (ADS) is responsible for the production of ornithine, CO2, ammonia, and ATP from arginine. The ADS of the oral bacterium Streptococcus gordonii plays major roles in physiologic homeostasis, acid tolerance, and oral biofilm ecology. To further our understanding of the transcriptional regulation of the ADS (arc) operon, the binding of the ArcR transcriptional activator, which governs expression of the ADS in response to arginine, was investigated by DNase I protection and gel mobility shift assays. An ArcR binding sequence was found that was 27 bp in length and had little sequence similarity to binding sites of other arginine metabolism regulators. The presence of arginine at physiologically relevant concentrations enhanced the binding of ArcR to its target. Using cat fusions, various deletion and substitution mutations within the putative ArcR footprint were shown to cause dramatic reductions in expression from the arcA promoter in vivo, confirming that the 27-bp sequence is required for optimal expression and induction of the ADS by arginine. Mutation of two putative catabolite response elements (CREs) within the arc promoter region showed that both CREs contribute to catabolite repression. A thorough understanding of the regulation of the ADS in S. gordonii and related organisms is needed to develop ways to exploit arginine catabolism for the control of oral diseases. Identification of the ArcR and CcpA binding sites lays the foundation for a more complete understanding of the complex interactions of multiple regulatory proteins with elements in the arc promoter region.

DNA, Bacterial↗

PubMed2006

[Measurement of personal noise exposure in a cold rolling mill].

OBJECTIVE: To measure and evaluate the personal noise exposure of cold rolling mill workers by using noise dosimeter. METHODS: According to job category and work type, all workers were divided into 11 groups. 3 to 5 day shift (8:00 to 16:00) workers from each group were selected as subjects for personal noise exposure measurement. SH-126 dosimeters were worn by each subject and collect noise data by a phone fix at collar. All subjects were asked to take notes about their working activities when they were wearing SH-126 dosimeters. Each worker's L(A)(eq) of 8 hours, geometric mean and range of each group were computed. RESULTS: There were many noise sources in the workshop. Recorded data showed that noise exposure of cold rolling mill was unstable. The varieties of personal noise levels were quite large. Among 53 workers, the highest noise exposure level was 100.0 dB (A), the lowest was 81.2 dB (A); the highest work type was of the foreside welders [94.20 dB (A)], and the lowest was of the straight-cutters [89.02 dB (A)]; quality checkers had the biggest rang [16.3 dB (A)], and primary rolling workers had the lest [2.3 dB (A)]. CONCLUSION: Noise exposure of all the 11 groups were more than 85 dB (A). Noise protection of these workers should be improved. It suggested that measuring personal noise exposure individually with dosimeters might obtain the noise exposure level more integrally in the complicated environment.

Environmental Monitoring↗

PubMed2006

[Relationship between sample size and variation of means for personal noise exposure in weaving workers].

OBJECTIVE: To explore the relationship between sample size and variance of means for personal noise exposure in weaving workers as to contributing evidence for establishing personal noise exposure measurement guideline. METHODS: A personal noise exposure measurement database from a group of weaving workers was used in the randomized re-sampling data analysis. The sampling cases were one number selecting from one to fifteen at each randomized re-sampling procedure. The randomized re-sampling was one thousand times from original personal noise exposure measurement database to get one thousands of re-sampling database. One thousands of L(Aeq.8 h) mean were calculated by re-sampling databases. The variation of randomized re-sampling means was analyzed for different re-sampling numbers. RESULTS: The change for narrow trend of maximum, minimum, 95 percent number, 5 percent number of L(Aeq.8 h) mean was faster when randomized re-sampling number was smaller in variation vs randomized re-sampling number curve analysis. After that, the change for narrow trend of L(Aeq.8 h) mean was smooth for increasing the randomized re-sampling numbers. The 95% - 5% of L(Aeq.8 h) mean was about half for randomized re-sampling four cases (3.30 dB) vs one case (7.40 dB), and about one third for seven cases (2.44 dB), and about one fourth for eleven cases (1.85 dB). CONCLUSION: The sample size in personal noise exposure measurement guideline could be selected from four to eleven.

Humans↗

PubMed2006

[The difference of nerve growth factor and ciliary neurotrophic factor between the sensitive and motor fibres regeneration].

OBJECTIVE: To investigate the effects of nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) to promoting the sensitive and motor fibres regeneration. METHODS: Thirty two Sprague-Dawley rats with 10 mm gap of sciatic nerve were operated and bridged with the new double channel nerve conduit in rhomboid shape. They were randomly divided into two groups, with each in twelve animals. In the first group, 200 micro1 of chitin for medical use was injected into the conduit, and in the second group the two branches of the conduit contained 100 microl of the chitin and 5 microl NGF or CNTF. At twelve and sixteen weeks after the operation, we evaluated the sensitive and motor fibres of regenerative nerve with Holmes, Acetylcholinesterase and Carbonic anhydrase staining. RESULTS: After the twelve and sixteen weeks of the operation, there were not significant differences of the regenerative nerve fibres between two channels in the first groups. But in the second group, the number of the motor fibres of the regenerative nerve of CNTF branch channel was much more and distributed better than the others, while the number and density of sensitive fibres was inferior to NGF. The latency of compound muscle active potential and cortical somatosensory evoked potential of the nerve in the CNTF branch was shorter than the one in the NGF branch, but its amplitude was higher. CONCLUSIONS: The CNTF could significantly promote the regeneration of motor fibres and the NGF could promote better for the regeneration of sensitive fibres.

Animals↗

PubMed2003

Regulation of membrane permeability by a two-component regulatory system in Pseudomonas aeruginosa.

Membrane impermeability is the major contributing factor to multidrug resistance in clinical isolates of Pseudomonas aeruginosa. By using laboratory strain PAK, a spontaneous P. aeruginosa mutant (mutant PAK1-3) whose membrane had reduced permeability and which displayed increased levels of resistance to various antibiotics, especially aminoglycosides, was isolated. By complementation of the mutant with a genomic clone library derived from wild-type strain PAK, a novel two-component regulatory system (PprA and PprB) was identified and was found to be able to increase the permeability of the bacterial membrane and render PAK1-3 sensitive to antibiotics. Furthermore, specific phosphorylation of the response regulator (PprB) by histidine kinase (PprA) was observed in vitro, demonstrating that they are cognate two-component regulatory genes. Introduction of a plasmid expressing the pprB gene into randomly chosen clinical isolates (n = 17) resulted in increased sensitivity to aminoglycosides in the majority of isolates (n = 13) tested. This is the first demonstration that P. aeruginosa membrane permeability can be regulated, providing an important clue in the understanding of the mechanism of membrane impermeability-mediated multidrug resistance in P. aeruginosa.

Cell Membrane Permeability↗

PubMed2003

aph(3')-IIb, a gene encoding an aminoglycoside-modifying enzyme, is under the positive control of surrogate regulator HpaA.

Pseudomonas aeruginosa harbors a chromosomal aminoglycoside phosphotransferase gene, aph(3')-IIb, which confers P. aeruginosa resistance to several important aminoglycoside antibiotics, including kanamycin A and B, neomycin B and C, butirosin, and seldomycin F5. The aph(3')-IIb gene has been found to be regulated by an AraC-type transcriptional regulator (HpaA) encoded by a gene located upstream of the aph(3')-IIb gene. In the presence of 4-hydroxyphenylacetic acid (4-HPA), HpaA activates the expression of aph(3')-IIb as well as that of the hpa regulon which encodes metabolic enzymes for the utilization of 4-HPA. hpaA and aph(3')-IIb form an operon, and in response to the presence of 4-HPA, the wild-type P. aeruginosa strain PAK (but not its hpaA mutant strain) displays increased resistance to neomycin. A survey of 39 clinical and 19 environmental isolates of P. aeruginosa demonstrated in all of them the presence of an hpaA-aph gene cluster, while 56 out of the 58 isolates are able to utilize the 4-HPA as a sole carbon source, suggesting a feature common to P. aeruginosa strains. Interestingly, a larger portion of clinical isolates than environmental isolates showed 4-HPA-induced resistance to neomycin. The aph(3')-IIb gene product is likely to function as a metabolic enzyme which has a cross-reactivity with aminoglycosides. These findings provide new insight into the possible mechanism of P. aeruginosa antibiotic resistance.

Amino Acid Sequence↗

PubMed2002

Experimental study on the apoptosis of the astrocytes and the oligodendrocytes induced by Ca(2+) reperfusion.

OBJECTIVE: To investigate the apoptosis rules of the astrocytes and oligodendrocytes induced by Ca(2+) reperfusion. METHODS: The apoptosis of purified cultured astrocytes and oligodendrocytes induced by Ca(2+) reperfusion and the relationship between the development of the cell apoptosis and post-reperfusion time was observed. RESULTS: Both the astrocytes and oligodendrocytes were obviously in a time-dependent fashion, and the apoptosis ratios of the oligodendrocytes (39.73%+/-4.16%) were higher than the astrocytes (19.64%+/-4.67%) 24 hours after Ca(2+) reperfusion. The TUNEL positive cells were 13.6+/-1.82 and 21.4+/-1.95 at every visual field of astrocytes and oligodendrocytes respectively 24 hours after Ca(2+) reperfusion. CONCLUSIONS: The astrocytes and oligodendrocytes are similar wi th the development rules on apoptosis and have different susceptiveness to the situation.

Animals↗

PubMed2002

Effect of nerve growth factor on changes of myelin basic protein and functional repair of peripheral nerve following sciatic nerve injury in rats.

OBJECTIVE: To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. METHODS: The sciatic nerves of rats were injured by sectioning with shaver,and divided into 3 groups: NGF group (Group A), group of normal saline solution (Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD-4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP. RESULTS: The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B (P<0.05). The MEP was elicited in 76% of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP-positive cells in the Group A than in the Group B in one and four weeks respectively. CONCLUSIONS: NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.

Animals↗

PubMed2000

Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of exoS.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that primarily infects immunocompromised individuals and patients with cystic fibrosis. Using a tissue culture system, invasive strains of P. aeruginosa were discovered to induce apoptosis at high frequency in HeLa and other epithelial and fibroblast cell lines. This apoptotic phenotype in the infected cells was determined by several criteria including (i) visual changes in cell morphology, (ii) induction of chromatin condensation and nuclear marginalization, (iii) the presence of a high percentage of cells with subG1 DNA content, and (iv) activation of caspase-3 activity. Induction of the type III secretion machinery, but not invasion of P. aeruginosa is required for induction of apoptosis. The apoptosis phenotype is independent of the cytoskeletal rearrangements that occur in the host cell early after infection. Mutants in P. aeruginosa exoS fail to induce apoptosis and complementation with wild-type exoS restored the apoptosis-inducing capacity, demonstrating that ExoS is the effector molecule. Analysis of exoS activity mutants shows that the ADP-ribosylating capacity of ExoS is essential for inducing the apoptotic pathway.

ADP Ribose Transferases↗