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Ling Lin

Publications and source records attributed to Ling Lin.

78 records · Page 5Linked to original sources
PubMed2002

Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and ACh.

Recent therapeutic investigations of Alzheimer's disease (AD) have been guided by two seemingly opposed hypotheses: the amyloid cascade theory, which favors the amyloid plaques as the cause of AD; and the cholinergic theory, which favors cholinergic neuron loss as the cause. New investigations indicate that the synthesis and processing of the amyloid precursor protein (APP) is linked to the trophic actions of nerve growth factor. A pathological cascade in both AD- and Down's syndrome-related memory loss could be triggered by alterations in APP processing or ACh-mediated neuronal function, or both, which in turn trigger the overexpression of amyloid beta, synaptic malfunction and trophic factor loss in target regions. This eventually leads to synaptic and dendritic loss with age.

Acetylcholine↗
PubMed2002

Comparative study of enterostatin sequence in five rat strains and enterostatin binding proteins in rat and chicken serum.

Enterostatin, a pentapeptide derived from the precursor protein procolipase has been shown to inhibit dietary fat intake and to reduce body fat after chronic administration in rats. We repeat that the enterostatin amino acid sequence from the genomic DNA of 5 different rat strains is APGPR. 125I-APGPR bound to three proteins (300, 205 and 60 kDa) in rat serum and one 60 kDa protein in chicken serum. These serum binding proteins were also eluted by APGPR affinity chromatography. Western blot analysis of serum protein identified enterostatin-like immunoreactivity associated with the same molecular weight bands. Our results demonstrate the enterostatin sequence in rat is APGPR and suggest the presence of enterostatin binding proteins in rat and chicken serum.

Animals↗
PubMed2002

Analysis of mitochondrial gene mutations in Chinese pedigrees of Leber's hereditary optic neuropathy.

PURPOSE: To investigate the frequency of common pathogenic primary mitochondrial DNA mutations in Leber's hereditary optic neuropathy (LHON) families. METHODS: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing were used to detect mitochondrial DNA mutations. Sixty-six Chinese examiners from 15 families, including 22 visual affected and their 44 unaffected maternal relatives, underwent molecular genetic evaluation. Eleven normal individuals underwent evaluation as control. RESULTS: Of the 15 families with suspicion of LHON, 13 had nucleotide position (nt) G11778A mutations, 2 had nt T14484C mutations. All examiners had nt G11719A mutations. CONCLUSIONS: The mutations at nucleotides 11778 and 14484 are primary LHON mutations. Molecular genetic findings suggest that the silent mutation at nt G11719A may be a common genetic polymorphism in Chinese.

Adolescent↗
PubMed2001

Synergistic cytotoxic effect between serine-threonine phosphatase inhibitors and 5-fluorouracil: a novel concept for modulation of cytotoxic effect.

PURPOSE: The present study was undertaken to look for an agent or agents able to modulate the cytotoxic effect of 5-fluorouracil (FUra) and to investigate the role of serine-threonine phosphatase inhibitors on the cytotoxic effect of FUra. METHODS: The cytotoxicities of FUra and protein phosphatase inhibitors (PPIs) were evaluated by two different methods: a clonogenic assay and a proliferation assay. In the clonogenic assay, cancer cells were treated with various concentration of FUra with or without PPIs for 72 h. The drug-containing medium was replaced by fresh medium, the cultures incubated for an additional 10 days, and the colonies enumerated. In the proliferation assay the cells were treated with FUra alone or in combination with PPIs for 96 h and cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay based on the uptake of the tetrazolium dye. Thymidine kinase (TK) activity was determined based on the catalytic phosphorylation of [(3)H]d-thymidine to [(3)H]dTMP. Incorporation of FUra into DNA and RNA was determined by treating the cells with [2-(14)C]fluorouracil for 72 h and measuring the radioactivity in the isolated DNA and RNA fractions. RESULTS: The serine-threonine phosphatase inhibitors caliculin A (CAL), okadaic acid (OA) and microcystin-LR (MCLR) dose-dependently inhibited the growth of Clone 20 and Clone 5 cells of Colon 26 murine colon adenocarcinoma cells, human cervical cancer HeLa cells, human gastric cancer MKN 7 cells, and murine sarcoma S-180 cells in vitro. Among the compounds tested, MCLR at non-toxic concentrations was found to increase FUra incorporation into RNA and DNA in Clone 20 cells by 60% and 127%, respectively, to increase TK activity alone (twofold) as well as in combination with FUra (threefold), and to potentiate the cytotoxicity of FUra synergistically and cytospecifically in vitro. The cytotoxicity of FUra alone or in combination with MCLR, but not that of PPIs alone, was abrogated almost completely by exogenous thymidine (dThd), suggesting that inhibition of thymidylate synthetase (TS) is the growth-limiting event in the cytotoxic action of FUra even in combination with MCLR. CONCLUSIONS: The findings presented here suggest that MCLR synergistically and cytospecifically potentiates the antitumor activity of FUra with substantial improvement in the therapeutic index of FUra via enhancement of both DNA- and RNA-directed cytotoxicity.

Animals↗
PubMedDate not supplied

Continuous increase in phosphorylation of cytosolic thymidine kinase during proliferation of rat hepatoma JB1 cells.

Thymidine kinase (TK) is a protein closely associated with DNA replication. Here we show that, in contrast with the variation of TK activity, which changed parallel with S phase cell distribution during asynchronous culture of rat hepatoma JB1 cells, the serine residues of cytosolic TK protein was phosphorylated continuously in response to increasing G0/G1 phase cell distribution. The shifting of phosphorylation of TK protein during different cell growth conditions was further confirmed with the examination of the elution profile of cytosolic TK activity by anion-exchange high performance liquid chromatography (HPLC). HPLC analysis revealed that the rapid proliferating (62 h after asynchronous culture) rat hepatoma JB1 cells showed only the hyperphosphorylated form of cytosolic TK activity, while synchronously M phase-arrested JB1 cells showed hypo- and hyper-phosphorylated forms of cytosolic TK activity. These results suggested that the modulation of phosphorylation of cytosolic TK protein was cell cycle-dependent, and that the phosphorylation of cytosolic TK protein might be involved in the negative regulation of TK activity in vivo.

Animals↗