Huang CC

References (13)

Title : Multi-Target Effects of Novel Synthetic Coumarin Derivatives Protecting Abeta-GFP SH-SY5Y Cells against Abeta Toxicity - Huang_2021_Cells_10_
Author(s) : Huang CC , Chang KH , Chiu YJ , Chen YR , Lung TH , Hsieh-Li HM , Su MT , Sun YC , Chen CM , Lin W , Lee-Chen GJ
Ref : Cells , 10 : , 2021
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease presenting with progressive memory and cognitive impairments. One of the pathogenic mechanisms of AD is attributed to the aggregation of misfolded amyloid beta (Abeta), which induces neurotoxicity by reducing the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TRKB) and increasing oxidative stress, caspase-1, and acetylcholinesterase (AChE) activities. Here, we have found the potential of two novel synthetic coumarin derivatives, ZN014 and ZN015, for the inhibition of Abeta and neuroprotection in SH-SY5Y neuroblastoma cell models for AD. In SH-SY5Y cells expressing the GFP-tagged Abeta-folding reporter, both ZN compounds reduced Abeta aggregation, oxidative stress, activities of caspase-1 and AChE, as well as increased neurite outgrowth. By activating TRKB-mediated extracellular signal-regulated kinase (ERK) and AKT serine/threonine kinase 1 (AKT) signaling, these two ZN compounds also upregulated the cAMP-response-element binding protein (CREB) and its downstream BDNF and anti-apoptotic B-cell lymphoma 2 (BCL2). Knockdown of TRKB attenuated the neuroprotective effects of ZN014 and ZN015. A parallel artificial membrane permeability assay showed that ZN014 and ZN015 could be characterized as blood-brain barrier permeable. Our results suggest ZN014 and ZN015 as novel therapeutic candidates for AD and demonstrate that ZN014 and ZN015 reduce Abeta neurotoxicity via pleiotropic mechanisms.
ESTHER : Huang_2021_Cells_10_
PubMedSearch : Huang_2021_Cells_10_
PubMedID: 34831318

Title : Novel synthetic chalcone-coumarin hybrid for Abeta aggregation reduction, antioxidation, and neuroprotection - Lee_2018_CNS.Neurosci.Ther_24_1286
Author(s) : Lee SY , Chiu YJ , Yang SM , Chen CM , Huang CC , Lee-Chen GJ , Lin W , Chang KH
Ref : CNS Neurosci Ther , 24 :1286 , 2018
Abstract : BACKGROUND: Aggregation of misfolded amyloid beta (Abeta) in senile plaques causes oxidative stress and neuronal death in Alzheimer's disease (AD). Compounds possessing antiaggregation and antioxidant properties are promising candidate compounds for AD treatment. METHODS: We examined the potential of synthetic derivatives of licochalcone A and coumarin for inhibiting Abeta aggregation, scavenging reactive oxygen species (ROS), and providing neuroprotection by using biochemical assays and Tet-On Abeta-GFP 293/SH-SY5Y cell models for AD. RESULTS: Among test compounds, LM-031, a novel chalcone-coumarin hybrid, inhibited Abeta aggregation and scavenged free oxygen radicals. LM-031 markedly reduced Abeta misfolding and ROS as well as promoted neurite outgrowth and inhibited acetylcholinesterase in Tet-On Abeta-GFP 293/SH-SY5Y cells. Mechanistic studies showed upregulation of the HSPB1 chaperone, NRF2/NQO1/GCLC pathway, and CREB/BDNF/BCL2 pathway. Decreased neurite outgrowth upon the induction of Abeta-GFP was rescued by LM-031, which was counteracted by knockdown of HSPB1, NRF2, or CREB. CONCLUSION: Taken together, these findings demonstrate that LM-031 exhibited antiaggregation, antioxidant, and neuroprotective effects against Abeta toxicity by enhancing HSPB1 and the NRF2-related antioxidant pathway as well as by activating the CREB-dependent survival and antiapoptosis pathway. These results imply that LM-031 may be a new therapeutic compound for AD.
ESTHER : Lee_2018_CNS.Neurosci.Ther_24_1286
PubMedSearch : Lee_2018_CNS.Neurosci.Ther_24_1286
PubMedID: 30596401

Title : Biocuration in the structure-function linkage database: the anatomy of a superfamily - Holliday_2017_Database.(Oxford)_2017_
Author(s) : Holliday GL , Brown SD , Akiva E , Mischel D , Hicks MA , Morris JH , Huang CC , Meng EC , Pegg SC , Ferrin TE , Babbitt PC
Ref : Database (Oxford) , 2017 : , 2017
Abstract : With ever-increasing amounts of sequence data available in both the primary literature and sequence repositories, there is a bottleneck in annotating molecular function to a sequence. This article describes the biocuration process and methods used in the structure-function linkage database (SFLD) to help address some of the challenges. We discuss how the hierarchy within the SFLD allows us to infer detailed functional properties for functionally diverse enzyme superfamilies in which all members are homologous, conserve an aspect of their chemical function and have associated conserved structural features that enable the chemistry. Also presented is the Enzyme Structure-Function Ontology (ESFO), which has been designed to capture the relationships between enzyme sequence, structure and function that underlie the SFLD and is used to guide the biocuration processes within the SFLD. Database URL:
ESTHER : Holliday_2017_Database.(Oxford)_2017_
PubMedSearch : Holliday_2017_Database.(Oxford)_2017_
PubMedID: 28365730

Title : A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons - Tervo_2016_Neuron_92_372
Author(s) : Tervo DG , Hwang BY , Viswanathan S , Gaj T , Lavzin M , Ritola KD , Lindo S , Michael S , Kuleshova E , Ojala D , Huang CC , Gerfen CR , Schiller J , Dudman JT , Hantman AW , Looger LL , Schaffer DV , Karpova AY
Ref : Neuron , 92 :372 , 2016
Abstract : Efficient retrograde access to projection neurons for the delivery of sensors and effectors constitutes an important and enabling capability for neural circuit dissection. Such an approach would also be useful for gene therapy, including the treatment of neurodegenerative disorders characterized by pathological spread through functionally connected and highly distributed networks. Viral vectors, in particular, are powerful gene delivery vehicles for the nervous system, but all available tools suffer from inefficient retrograde transport or limited clinical potential. To address this need, we applied in vivo directed evolution to engineer potent retrograde functionality into the capsid of adeno-associated virus (AAV), a vector that has shown promise in neuroscience research and the clinic. A newly evolved variant, rAAV2-retro, permits robust retrograde access to projection neurons with efficiency comparable to classical synthetic retrograde tracers and enables sufficient sensor/effector expression for functional circuit interrogation and in vivo genome editing in targeted neuronal populations. VIDEO ABSTRACT.
ESTHER : Tervo_2016_Neuron_92_372
PubMedSearch : Tervo_2016_Neuron_92_372
PubMedID: 27720486

Title : Rheumatoid Arthritis Was Negatively Associated with Alzheimer's Disease: A Population-Based Case-Control Study - Kao_2016_PLoS.One_11_e0168106
Author(s) : Kao LT , Kang JH , Lin HC , Huang CC , Lee HC , Chung SD
Ref : PLoS ONE , 11 :e0168106 , 2016
Abstract : Some of the prior literature investigated the potential association between rheumatoid arthritis (RA) and Alzheimer's disease (AD) because these two diseases may share similar inflammatory mechanisms. Nevertheless, to date, findings of the previous literature are still controversial, and some methodological limitations were observed in those studies. The aim of this case-control study was to investigate the relationship between prior RA and AD using a large population-based dataset. This study used the Taiwan Longitudinal Health Insurance Database 2005. We included 2271 patients with AD who had received prescriptions for acetylcholinesterase inhibitors (AChEIs) as cases and 6813 patients without AD as controls in this study. In addition, we performed a conditional logistic regression to examine the odds ratio (OR) and 95% confidence interval (CI) for prior RA between cases and controls. The study found that 330 (3.63%) of the total sampled patients had an RA diagnosis before the index date. Additionally, prior RA was found in 60 (2.64%) cases and in 270 (3.96%) controls. The conditional logistic regression analysis showed that the crude OR of prior RA for cases was 0.66 (95% confidence interval (CI): 0.49~0.87) compared to controls. After adjusting for patients' geographic location, urbanization level, and comorbidities, the adjusted OR of prior RA for patients with AD was 0.73 (95% CI: 0.55~0.98) compared to those without AD. We concluded that there was an inverse association between prior RA and AD even after adjusting for potential confounders.
ESTHER : Kao_2016_PLoS.One_11_e0168106
PubMedSearch : Kao_2016_PLoS.One_11_e0168106
PubMedID: 27997574

Title : Soluble epoxide hydrolase inhibitor enhances synaptic neurotransmission and plasticity in mouse prefrontal cortex - Wu_2015_J.Biomed.Sci_22_94
Author(s) : Wu HF , Yen HJ , Huang CC , Lee YC , Wu SZ , Lee TS , Lin HC
Ref : J Biomed Sci , 22 :94 , 2015
Abstract : BACKGROUND: The soluble epoxide hydrolase (sEH) is an important enzyme chiefly involved in the metabolism of fatty acid signaling molecules termed epoxyeicosatrienoic acids (EETs). sEH inhibition (sEHI) has proven to be protective against experimental cerebral ischemia, and it is emerging as a therapeutic target for prevention and treatment of ischemic stroke. However, the role of sEH on synaptic function in the central nervous system is still largely unknown. This study aimed to test whether sEH C-terminal epoxide hydrolase inhibitor, 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) affects basal synaptic transmission and synaptic plasticity in the prefrontal cortex area (PFC). Whole cell and extracellular recording examined the miniature excitatory postsynaptic currents (mEPSCs) and field excitatory postsynaptic potentials (fEPSPs); Western Blotting determined the protein levels of glutamate receptors and ERK phosphorylation in acute medial PFC slices.
RESULTS: Application of the sEH C-terminal epoxide hydrolase inhibitor, AUDA significantly increased the amplitude of mEPSCs and fEPSPs in prefrontal cortex neurons, while additionally enhancing long term potentiation (LTP). Western Blotting demonstrated that AUDA treatment increased the expression of the N-methyl-D-aspartate receptor (NMDA) subunits NR1, NR2A, NR2B; the alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR1, GluR2, and ERK phosphorylation.
CONCLUSIONS: Inhibition of sEH induced an enhancement of PFC neuronal synaptic neurotransmission. This enhancement of synaptic neurotransmission is associated with an enhanced postsynaptic glutamatergic receptor and postsynaptic glutamatergic receptor mediated synaptic LTP. LTP is enhanced via ERK phosphorylation resulting from the delivery of glutamate receptors into the PFC by post-synapse by treatment with AUDA. These findings provide a possible link between synaptic function and memory processes.
ESTHER : Wu_2015_J.Biomed.Sci_22_94
PubMedSearch : Wu_2015_J.Biomed.Sci_22_94
PubMedID: 26494028

Title : Effects of long-term ethanol consumption on jejunal lipase and disaccharidase activities in male and female rats - Huang_2005_World.J.Gastroenterol_11_2603
Author(s) : Huang CC , Chen JR , Liu CC , Chen KT , Shieh MJ , Yang SC
Ref : World J Gastroenterol , 11 :2603 , 2005
Abstract : AIM: To study the effect of long-term ethanol consumption on jejunal lipase and disaccharidase (sucrase, maltase, and lactase) activities in rats and its gender difference.
METHODS: Age-matched male and female Wistar rats were fed control or ethanol-containing liquid diets for 12 wk following the Lieber-DeCarli model. According to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, 40 rats were divided into four groups as follows: male control group (MC), male ethanol group (ME), female control group (FC), and female ethanol group (FE).
RESULTS: After ethanol feeding for 12 wk, the results revealed that plasma AST and ALT activities of group ME were significantly increased by 58% and 92%, respectively, than those of group MC (P<0.05). Similarly, plasma AST and ALT activities of group FE were also significantly increased by 61% and 188%, respectively, than those of group FC (P<0.05). Fat accumulation was observed in both ethanol-treated groups, while fatty changes were more severe in group FE than those in group ME. The induction of hepatic microsomal cytochrome P450 2E1 (CYP2E1) was obviously seen in group ME and group FE, but was not detected in group MC and group FC. Jejunal lipase activity of group ME was significantly increased by 1.25-fold than that of group MC (P<0.05). In contrast to, sucrase, maltase, and lactase activities of group ME were significantly decreased by 63%, 62% and 67%, respectively, than those of group MC (P<0.05). Similarly, activities of these three enzymes of group FE were also significantly decreased by 43%, 46% and 52%, respectively, than those of group FC (P<0.05). There were no significant epithelial changes of the duodenal mucosa in any group. CONCLUSION: Long-term ethanol consumption significantly can increase jejunal lipase and decrease jejunal disaccharidase activities in both male and female rats.
ESTHER : Huang_2005_World.J.Gastroenterol_11_2603
PubMedSearch : Huang_2005_World.J.Gastroenterol_11_2603
PubMedID: 15849819

Title : Most common intoxication in nephrology ward organophosphate poisoning - Lin_2004_Ren.Fail_26_349
Author(s) : Lin CL , Yang CT , Pan KY , Huang CC
Ref : Ren Fail , 26 :349 , 2004
Abstract : OBJECTIVES: In Taiwan, the widespread use of organophosphates (OPs) in agricultural and household environments results in numerous OP poisoning. To better understand the clinical significance of associated parameters on respiratory failure and patient outcome, we evaluate patients admitted to the Nephrology ward in our hospital with OP intoxication. PATIENTS AND
METHODS: Over a period of 2 years, a total of 42 consecutive patients with OP poisoning admitted to the nephrology ward or the Intensive Care Unit of Chang-Gung Memorial Hospital were the subjects in the study. The diagnosis of poisoning was based on history of ingestion and characteristic clinical features of anticholinesterase agent poisoning. Prior to treatment, all symptoms recorded at emergency room and blood samples for blood chemistry including plasma amylase and plasma acetyl-cholinesterase were collected from each patient immediately after the admission.
RESULTS: As clinical manifestations of OP show, nausea and vomiting and salivation were the leading manifestations, 45.2% and 33.3%, respectively. Patients who developed respiratory failure were older than those who did not (54.3+/-6.9 vs. 43.1+/-5.6, p<0.05). The dosage of atropine administered for treatment was significantly higher in the patient group with respiratory failure compared to those without respiratory failure (29.7+/-14.5 vs. 9.1+/-10.2, p<0.05). Plasma amylase level of the patient group with respiratory failure was significantly higher than those without respiratory failure (436.1+/-87.1 vs. 181.3+/-29.6, p<0.01). Of course, mean days of hospitalization in the respiratory failure group are significantly longer than the other group (12.1+/-2.1 vs. 5.4+/-1.9, p<0.05). Based on univariant analysis, bradycardia, hypotension, fasciculation and coma were significant factors associated with respiratory failure. The dose of atropine administered for treatment was significantly higher in the oral exposure group compared to nonoral exposure group (23.6+/-12.6 vs. 10.6+/-6.4, p<0.05). The same is true for the pralidoxime treatment (9.6+/-1.9 vs. 5.3+/-1.4, p<0.05). As for mean days of hospitalization (11.6+/-3.9 vs. 6.4+/-2.1, p<0.05) and fatality (2 vs. 0, p<0.05), those of oral exposure patients were significantly longer and higher than those with nonoral exposure.
CONCLUSIONS: We demonstrate that elevated plasma amylase concentration was related to the development of respiratory failure in OP intoxication. It also provided us various important risk factors to identify those patients with OP poisoning who would ultimately require ventilatory support.
ESTHER : Lin_2004_Ren.Fail_26_349
PubMedSearch : Lin_2004_Ren.Fail_26_349
PubMedID: 15462100

Title : Investigations on the mechanism of tetrahydro-9-aminoacridine-induced presynaptic inhibition in the rat amygdala - Wang_1996_Neurosci_70_409
Author(s) : Wang SJ , Huang CC , Gean PW
Ref : Neuroscience , 70 :409 , 1996
Abstract : Tetrahydro-9-aminoacridine, a centrally acting anticholinesterase, has been reported to improve clinical conditions of certain patients with Alzheimer's disease. A previous study from our laboratory suggested that tetrahydro-9-aminoacridine presynaptically inhibited synaptic transmission. In the present study, the mechanism responsible for presynaptic inhibition mediated by tetrahydro-9-aminoacridine was studied in the rat amygdalar slice preparation using intracellular recording techniques. Bath application of tetrahydro-9-aminoacridine reversibly suppressed the excitatory postsynaptic potential. Tetrahydro-9-aminoacridine's inhibitory action was unaffected by the pretreatment of slices with baclofen (5 microM), suggesting that it did not act by eliciting the release of GABA, which binds presynaptic GABAB receptors to inhibit glutamate release. The synaptic depressant effect of tetrahydro-9-aminoacridine was blocked in the presence of 4-aminopyridine. The action of 4-aminopyridine could be reversed by reducing extracellular Ca2+ concentrations from a control level of 2.5 to 0.5 mM, suggesting that tetrahydro-9-aminoacridine inhibits excitatory postsynaptic potentials by acting directly at the terminals to decrease a Ca2+ influx. The L-type Ca2+ channel blocker nifedipine (50 microM) had no effect on tetrahydro-9-aminoacridine-induced presynaptic inhibition. However, the depressant effect of tetrahydro-9-aminoacridine was partially occluded in slices pretreated with the N-type Ca2+ channel blocker omega-conotoxin GVIA (1 microM). It is concluded that a reduction in omega-conotoxin GVIA-sensitive Ca2+ currents contributes to tetrahydro-9-aminoacridine-mediated presynaptic inhibition. After exposure to bicuculline, a GABAA receptor antagonist, afferent stimulation evoked epileptiform bursts. Occasionally, spontaneous bursts similar in waveform to synaptically triggered bursts also occurred in disinhibited slices. Application of tetrahydro-9-aminoacridine reversibly reduced the burst duration in a concentration-dependent manner. These results suggest that tetrahydro-9-aminoacridine possesses anticonvulsant activity against disinhibited bursts.
ESTHER : Wang_1996_Neurosci_70_409
PubMedSearch : Wang_1996_Neurosci_70_409
PubMedID: 8848149

Title : Blockade of isoproterenol-induced synaptic potentiation by tetra-9-aminoacridine in the rat amygdala - Wang_1996_Neurosci.Lett_214_87
Author(s) : Wang SJ , Huang CC , Hsu KS , Tsai JJ , Gean PW
Ref : Neuroscience Letters , 214 :87 , 1996
Abstract : The effects of tetrahydro-9-aminoacridine (THA) on beta-adrenoceptor activation-induced synaptic potentiation were studied in brain slices of the rat amygdala using intracellular recording techniques. To exclude the involvement of N-methyl-D-aspartate (NMDA) receptors, all the experiments were performed in the presence of NMDA receptor antagonist, D-APV (50 microM). Bath application of isoproterenol (Iso; 15 microM) results in a long-lasting enhancement of the amplitude of excitatory postsynaptic potentials (EPSPs) to 200 +/- 6% of baseline. Forskolin, which directly activates adenyl cyclase, produces a similar effect suggesting that Iso may act through a cyclic AMP-dependent mechanism. Pretreatment of the slices with THA (300 microM) completely abolishes the Iso- and forskolin-induced synaptic potentiation. We hypothesize that the locus of THA/beta-adrenoceptor interaction is presynaptic; the underlying mechanism is likely due to THA's depression of transmitter release via a presynaptic blockade of voltage-dependent Ca2+ channels.
ESTHER : Wang_1996_Neurosci.Lett_214_87
PubMedSearch : Wang_1996_Neurosci.Lett_214_87
PubMedID: 8878090

Title : Distribution of tacrine and metabolites in rat brain and plasma after single- and multiple-dose regimens. Evidence for accumulation of tacrine in brain tissue - McNally_1996_Drug.Metab.Dispos_24_628
Author(s) : McNally WP , Pool WF , Sinz MW , Dehart P , Ortwine DF , Huang CC , Chang T , Woolf TF
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 24 :628 , 1996
Abstract : Tacrine [1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate (THA), Cognex] is a potent acetylcholinesterase inhibitor recently approved for treatment of mild-to-moderate Alzheimer's disease. The potential for THA and/or a metabolite of THA to accumulate in brain tissue was investigated by autoradiographic and metabolic profiling techniques in rats given single and multiple doses of [14C]THA. In addition, the brain-to-plasma distribution time course of orally administered 1-hydroxy-THA (1-OH-THA, 24 mg/kg), a primary rat metabolite with anticholinesterase activity, was also examined. Results from a 16 mg/kg single-dose study showed THA to cross the blood-brain barrier readily and concentrate in brain tissue, approximately 5-fold compared with plasma. The metabolite 1-OH-THA was found in much lower amounts relative to THA and when given separately at a similar dose the levels in brain tissue were comparable with plasma concentrations. After multiple-dose administration, THA concentrations in brain tissue were approximately 3-fold higher than those achieved after a single oral dose. However, concentration of 1-OH-THA metabolite increased only 50%. These data suggest a marked difference between the ability of THA and 1-OH-THA to accumulate in brain tissue and may reflect differences in lipophilicity as estimated by calculated log p values. The relevance of THA accumulation in brain tissue to delays observed in THA clinical management of Alzheimer's disease remains to be established.
ESTHER : McNally_1996_Drug.Metab.Dispos_24_628
PubMedSearch : McNally_1996_Drug.Metab.Dispos_24_628
PubMedID: 8781777

Title : Tetrahydro-9-aminoacridine presynaptically inhibits glutamatergic transmission in the rat amygdala - Wang_1995_Brain.Res.Bull_37_325
Author(s) : Wang SJ , Huang CC , Gean PW
Ref : Brain Research Bulletin , 37 :325 , 1995
Abstract : The effect of the centrally active anticholinesterase inhibitor tetrahydro-9-aminoacridine (THA) on synaptic transmission was studied in rat amygdala neurons in the in vitro slice preparation. THA reversibly suppressed the excitatory postsynaptic potential (EPSP) in a concentration-dependent manner. Postsynaptic depolarization induced by alpha-amino-5-methyl-4-isoxazole propionate (AMPA) was not decreased by THA. These results demonstrate that THA has a presynaptic inhibitory action on the physiology of synaptic transmission in the amygdala. Pretreating the slices with atropine did not affect THA's effect, indicating that the presynaptic muscarinic receptors are not involved.
ESTHER : Wang_1995_Brain.Res.Bull_37_325
PubMedSearch : Wang_1995_Brain.Res.Bull_37_325
PubMedID: 7542994

Title : Sister-chromatid exchanges and cell-cycle delay in Chinese hamster V79 cells treated with 9 organophosphorus compounds (8 pesticides and 1 defoliant) - Chen_1982_Mutat.Res_103_307
Author(s) : Chen HH , Sirianni SR , Huang CC
Ref : Mutat Res , 103 :307 , 1982
Abstract : Significant increase of sister-chromatid exchanges (SCE) in V79 cells treated with 2 organophosphorus pesticides (OPP), fenthion and oxydemeton-methyl, was observed. The other 7 compounds (6 OPP and 1 defoliant) namely, amaze, azinphos-methyl, bolstar, DEF-defoliant, fensulfothion, monitor and nemacur caused no increase of SCE frequencies at the doses tested. All the compounds except fensulfothion and oxydemeton-methyl induced cell-cycle delay in varying degrees. Cell-cycle delay caused by an OPP was found to be dose-dependent. Based on these data as well as others reported, it would appear that OPP which induce no SCE increase and no or slight cell-cycle delay could be considered as good candidates to substitute the pesticides that have been found to be harmful to the environment.
ESTHER : Chen_1982_Mutat.Res_103_307
PubMedSearch : Chen_1982_Mutat.Res_103_307
PubMedID: 6211614