Biomedical subjects

Gang Hu

Publications and source records attributed to Gang Hu.

At least 19 recordsLinked to original sources

PubMed2006

Aquaporin 4 regulates the effects of ovarian hormones on monoamine neurotransmission.

Aquaporin 4 (AQP4) is the predominant water channels in the brain of mammals. Our previous study has reported that AQP4 knockout induced sex-specific alterations in neurotransmission, indicating that AQP4 might regulate the interaction between sex hormones and neurotransmission. In the present study, we found that AQP4 knockout decreased the concentrations of estrogen and progestogen. Further study showed that exogenous estrogen decreased DA and 5-HT in cortex, reduced DA and 5-HT in striatum, but increased 5-HT in hippocampus in AQP4+/+ male mice. However, in AQP4-/- male mice, exogenous estrogen almost did not alter the levels of neurotransmitters except for decreasing DA in cortex. In female mice, ovariectomy decreased DA in the striatum of AQP4+/+ mice, but did not alter the levels of DA in AQP4-/- mice. These findings reveal for the first time that AQP4 regulates not only water and ion homeostasis but also the functions of ovarian hormone and neurotransmitter.

Animals↗

PubMed2006

EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration.

AQP3 (aquaporin-3), known as an integral membrane channel in epidermal keratinocytes, facilitates water and glycerol movement into and out of the skin. Here, we demonstrate that AQP3 is also expressed in cultured human skin fibroblasts, which under normal wound healing processes migrate from surrounding tissues to close the wound. EGF (epidermal growth factor), which induced fibroblast migration, also induced AQP3 expression in a time- and dose-dependent manner. CuSO4 and NiCl2, previously known as AQP3 water transport inhibitors, as well as two other bivalent heavy metals Mn2+ and Co2+, inhibited EGF-induced cell migration in human skin fibroblasts. AQP3 knockdown by small interfering RNA inhibited EGF-induced AQP3 expression and cell migration. Furthermore, an EGFR (EGF receptor) kinase inhibitor, PD153035, blocked EGF-induced AQP3 expression and cell migration. MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK inhibitor U0126 and PI3K (phosphoinositide 3-kinase) inhibitor LY294002 also inhibited EGF-induced AQP3 expression and cell migration. Collectively, our findings show for the first time that AQP3 is expressed in human skin fibroblasts and that EGF induces AQP3 expression via EGFR, PI3K and ERK signal transduction pathways. We have provided evidence for a novel role of AQP3 in human skin fibroblast cell migration, which occurs during normal wound healing.

Aquaporin 3↗

PubMed2006

Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes.

The role of aquaporin-4 in water transport has been extensively investigated, while little information exists regarding its contribution to astrocytic functions such as the action to glutamatergic transmission. Since aquaporin-4 has been detected widely co-localized with glutamate transporter 1 (GLT-1) and glutamate transporters also present water transport properties, we investigated the regulative role of aquporin-4 on glutamate transporter using primary cultured astrocytes from aquaporin-4 knockout (AQP4(-/-)) mice. It was demonstrated that lack of aquaporin-4 down-regulated astrocytic expression of GLT-1 but not of glutamate/aspartate transporter (GLAST). The result from [(3)H]D,L-glutamate uptake analysis showed a lower uptake capability in AQP4(-/-) astrocytes. Furthermore, MTT and LDH assays indicated less cellular toxicity induced by excessive glutamate in AQP4(-/-) genotype. These findings provide direct evidences for the first time that aquaporin-4 plays an important role in the function of glutamate transporters. And the present study will improve our understanding of aquaporin-4-glutamanergic biology.

Animals↗

PubMed2006

Iptakalim protects PC12 cell against H2O2-induced oxidative injury via opening mitochondrial ATP-sensitive potassium channel.

The final common pathway in the demise of dopaminergic neurons in Parkinson's disease may involve oxidative stress and excitotoxicity. In this study, we examined the neuroprotective effects of a novel ATP-sensitive potassium channel (K(ATP)) opener, iptakalim (IPT), against H(2)O(2)-induced cytotoxicity in rat dopaminergic PC12 cells. Pretreatment with IPT could attenuate increased extracellular glutamate levels and inhibit calcium influxing induced by H(2)O(2). Moreover, IPT regulated the expressions of bcl-2 and bax which were responsible for inhibiting apoptosis in PC12 cells. These protective effects of IPT were abolished by selective mitoK(ATP) channel blocker 5-hydroxydecanoate. Therefore, IPT can protect PC12 cells against H(2)O(2)-induced oxidative injury via activating mitoK(ATP) channel.

Adenosine Triphosphate↗

PubMed2006

Occupational, commuting and leisure-time physical activity in relation to coronary heart disease among middle-aged Finnish men and women.

OBJECTIVE: To examine the association of different levels of occupational, commuting, and leisure-time physical activity with the risk of coronary heart disease (CHD) events. METHODS AND RESULTS: The study comprised 47,840 Finnish participants aged 25-64 years without history of CHD and stroke at baseline. During a mean follow-up of 18.9 years, 4660 new CHD events were documented. The multivariable-adjusted (age, body mass index, systolic blood pressure, total cholesterol, education, alcohol consumption, smoking, history of diabetes, and other two types of physical activity) hazard ratios (HRs) of CHD events associated with low, moderate, and high occupational activity were 1.00, 0.87, and 0.90 (P(trend)=0.019) for men, and 1.00, 0.75, and 0.80 (P(trend)<0.001) for women, respectively. The multivariable-adjusted HRs of CHD events associated with low, moderate, and high leisure-time physical activity were 1.00, 0.95, and 0.84 (P(trend)=0.026) for men, and 1.00, 0.85, and 0.77 (P(trend)=0.003) for women, respectively. Active commuting had a significant inverse association with the risk of CHD events in women but not in men. CONCLUSION: Moderate or high levels of occupational or leisure-time physical activity are associated with a reduced risk of CHD. Daily walking or cycling to and from work is associated with a decreased risk of CHD among women.

Adult↗

PubMed2006

Expression and colocalization of NADPH-diaphorase and Fos in the subnuclei of the parabrachial nucleus in rats following visceral noxious stimulation.

To investigate whether neural nitric oxide synthase (nNOS) in the parabrachial nucleus (PB) is involved in processing visceral noxious stimulation, we mapped the distribution of histochemical staining for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a marker for nNOS, and immunohistochemical staining for Fos, a neuronal activity marker, in the subnuclei of the PB following 2% formalin injection into the stomach of rats. NADPH-d and noxious-stimuli induced Fos staining were also examined in tissue containing PB cells labeled by the retrograde transport of fluogold (FG) injected into the central nucleus of the amygdala (CeA). We found that the number of Fos immunoreactive (Fos-IR) neurons was significantly increased in the dorsal lateral (dl), external lateral (el) and Kölliker-Fuse (KF) subnuclei of the PB. We observed that intensely labeled (type 1) NADPH-d positive neurons were mainly located in the rostral part of the PB; they extended long processes adjacent Fos-IR neurons, but no Fos/type 1 NADPH-d double-labeled neurons were seen. In contrast, lightly labeled (type 2) NADPH-d positive neurons were principally localized in the dl of the PB, in which a few Fos/type 2 NADPH-d double-labeled neurons were detected. Additionally, a large number of FG/Fos double-labeled neurons were observed to be surrounded closely by the intensive NADPH-d staining in the el of the PB. These results suggest that neurons in the el of the PB that project to the CeA are activated by visceral noxious stimulation and could be indirectly influenced by nitric oxide in the PB.

Analysis of Variance↗

PubMed2006

Activation of Group II/III metabotropic glutamate receptors attenuates LPS-induced astroglial neurotoxicity via promoting glutamate uptake.

Altered glial function that leads to oxidative stress and excitotoxicity may contribute to the initiation or progression of neuronal death in neurodegenerative diseases. We report the pivotal role of astroglial Group II and III metabotropic glutamate receptors (mGluR) against neurotoxicity. Activation of Group II or III mGluR on astrocytes with selective agonists DCG-IV or L-AP4 respectively inhibited astroglial lipopolysaccharide (LPS)-conditioned medium induced apoptosis of primary cultured mesencephalic neurons. Specific Group II or III mGluR antagonists APICA or MSOP completely abolished the neuroprotective effects of DCG-IV and L-AP4. Morphologic analysis showed that DCG-IV or L-AP4 could also attenuate the astroglial neurotoxicity to dopaminergic neurons. Measurement of extracellular glutamate concentration and [(3)H]-glutamate uptake showed that the restoration of glutamate uptake capability in LPS-treated astrocytes might be involved in the neuroprotective effects of activating astroglial Group II or III mGluR. Furthermore, we found that the repression of astroglial uptake function could be revived by GSH, and both Group II and III mGluR agonists could recover the endogenous reduced glutathione (GSH) level in LPS-treated astrocytes. These results suggested that the possible mechanisms of neuroprotection by either Type II or Type III mGluR activation may involve restoration of endogenous GSH, in turn affording recovery of astroglial capability to take up glutamate.

Animals↗

PubMed2006

Self-organization of chaos synchronization and pattern formation in coupled chaotic oscillators.

Pattern formation in spatiotemporal chaotic systems is investigated. Temporally chaotic and spatially ordered patterns are observed by varying the coupling strength. Spatial orderings emerge spontaneously due to self-organization of partial and nonlocal chaos synchronization, governed by various types of spatial symmetries. The first and secondary bifurcations from spatially disordered chaos to chaos with different levels of spatial orderings are observed and the scaling behaviors associated with these bifurcations are statistically analyzed.

Journal Article↗

PubMed2006

Novel allosteric properties produced by residue substitutions in the subunit interface of yeast NAD+-specific isocitrate dehydrogenase.

Yeast NAD+-specific isocitrate dehydrogenase (IDH) is an octamer of four IDH1 and four IDH2 subunits, and the basic structural unit of the enzyme is an IDH1/IDH2 heterodimer. To investigate one aspect of the interaction between IDH1 and IDH2, residues in a hydrophobic region at the heterodimer interface (Val-216, Ser-220, and Val-224 in IDH1; Ile-221, Val-225, and Val-229 in IDH2) were replaced by alanine residues in each and in both subunits. Gel filtration and sedimentation velocity analyses demonstrated that the residue substitutions do not disrupt the octameric structure of IDH. However, these substitutions produce novel kinetic properties including, with respect to cofactor, positive allosteric regulation by AMP and cooperativity in the absence of AMP. These allosteric properties are also apparent in NAD+-binding experiments. Despite substantial measurable activity for the mutant enzyme containing residue substitutions in both subunits, expression of this enzyme produces growth phenotypes indicative of IDH dysfunction in vivo.

Amino Acid Sequence↗

PubMed2006

Iptakalim modulates ATP-sensitive K(+) channels in dopamine neurons from rat substantia nigra pars compacta.

Iptakalim, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, exerts neuroprotective effects on dopaminergic (DA) neurons against metabolic stress-induced neurotoxicity, but the mechanisms are largely unknown. Here, we examined the effects of iptakalim on functional K(ATP) channels in the plasma membrane (pm) and mitochondrial membrane using patch-clamp and fluorescence-imaging techniques. In identified DA neurons acutely dissociated from rat substantia nigra pars compacta (SNc), both the mitochondrial metabolic inhibitor rotenone and the sulfonylurea receptor subtype (SUR) 1-selective K(ATP) channel opener (KCO) diazoxide induced neuronal hyperpolarization and abolished action potential firing, but the SUR2B-selective KCO cromakalim exerted little effect, suggesting that functional K(ATP) channels in rat SNc DA neurons are mainly composed of SUR1. Immunocytochemical staining showed a SUR1-rather than a SUR2B-positive reaction in most dissociated DA neurons. At concentrations between 3 and 300 microM, iptakalim failed to hyperpolarize DA neurons; however, 300 microM iptakalim increased neuronal firing. In addition, iptakalim restored DA neuronal firing during rotenone-induced hyperpolarization and suppressed rotenone-induced outward current, suggesting that high concentrations of iptakalim close neuronal K(ATP) channels. Furthermore, in human embryonic kidney 293 cells, iptakalim (300-500 microM) closed diazoxide-induced Kir6.2/SUR1 K(ATP) channels, which were heterologously expressed. In rhodamine-123-preloaded DA neurons, iptakalim neither depolarized mitochondrial membrane nor prevented rotenone-induced mitochondrial depolarization. These data indicate that iptakalim is not a K(ATP) channel opener in rat SNc DA neurons; instead, iptakalim is a pm-K(ATP) channel closer at high concentrations. These effects of iptakalim stimulate further pharmacological investigation and the development of possible therapeutic applications.

ATP-Binding Cassette Transporters↗

PubMed2006

Aquaporin-4 knockout regulated cocaine-induced behavior and neurochemical changes in mice.

Aquaporin-4 (AQP4) is the predominant water channel of brain, which mediates transmembrane water movement at the blood-brain barrier and at the brain-cerebrospinal fluid interface. It has been reported that AQP4 deletion results in an increase of amino acid and monoamine levels in some brain regions of mice, suggesting that AQP4 may participate in region-specific alterations in brain amino acid and monoamine metabolism. In the present study, we examined whether AQP4 affects neurotransmission in acute and chronic cocaine exposure mice. For this purpose, both wild-type and AQP4 knockout mice were used with locomotor activity evaluation and microdialysis methods. The results reveal that AQP4 deletion attenuated locomotor activity in acute and repeated cocaine exposure mice, and induced a decrease of extracellular dopamine and glutamate levels in the nucleus accumbens (NAc), a brain region known to be critically involved in the addictive properties of cocaine. Therefore, AQP4 may play a role in regulating extracellular cocaine-induced dopamine and glutamate release in the brain reward center, and in turn AQP4 deletion may attenuate cocaine reinforcement and dependence.

Animals↗

PubMed2006

Suppression of Winfree turbulence under weak spatiotemporal perturbation.

Winfree turbulence is a chaotic wave pattern developing through negative-tension instability of scroll wave filaments in three-dimensional weak excitable media. Here, we investigate the response of Winfree turbulence to a spatiotemporal forcing in the form of a traveling-wave modulation of the medium excitability. It is shown that turbulent waves can be suppressed much more rapidly by this method, in comparison with the space-uniform modulation of the medium excitability. Since the occurrence of Winfree turbulence is currently regarded as one of the possible mechanisms underlying cardiac fibrillation, this method turns out to be suggestive of a possible low-amplitude defibrillation approach.

Journal Article↗

PubMed2006

Iptakalim alleviated the increase of extracellular dopamine and glutamate induced by 1-methyl-4-phenylpyridinium ion in rat striatum.

The present study examined the effect of iptakalim (Ipt), a novel ATP-sensitive potassium (K(ATP)) channel opener (KCO), on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced dopamine (DA) and glutamate efflux in extracellular fluid of rat striatum, using microdialysis technique. Rats were implanted guide cannula in the striatum and artificial cerebrospinal fluid was infused through a microdialysis probe to detect the level of DA and glutamate in the striatum. MPP(+) significantly enhanced the extracellular levels of DA and its metabolites, DOPAC and HVA, as well as glutamate. Application of Ipt (1, 10, 100 microM) concentration-dependently suppressed DA and its metabolites efflux induced by MPP(+). Concomitantly, Ipt reduced the increase of extracellular glutamate induced by MPP(+). These results suggest that Ipt can regulate DA and glutamate efflux induced by MPP(+) in rat striatum.

1-Methyl-4-phenylpyridinium↗

PubMed2006

Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women.

AIMS: Serum gamma-glutamyltransferase (GGT) concentration may be involved in atherosclerosis. This study examined if serum GGT predicted coronary heart disease (CHD), especially differentiating non-fatal myocardial infarction (MI) and fatal CHD event, among the general population or participants with type-2 diabetes. METHODS AND RESULTS: A prospective study of 28,838 Finnish men and women aged 25-74 years was performed (1467 incident CHD cases; a median follow-up time of 11.9 years). Serum GGT cutpoints were the 25th, 50th, 75th, and 90th sex-specific percentiles. After adjustment for known cardiovascular risk factors, compared with the lowest GGT category, hazard ratios (HR) were 1.15, 1.25, 1.27, and 1.57 among men and 1.03, 1.22, 1.32, and 1.44 among women in other four GGT categories (P for trend <0.01, respectively). However, stronger associations were observed among subjects aged <60 and among alcohol drinkers. The strength of association was similar for non-fatal MI and for fatal CHD. Among subjects with type-2 diabetes, the corresponding adjusted HRs were 1.29, 1.57, 1.88, and 1.78 (P trend=0.03, men and women combined). CONCLUSION: This study suggests an independent mechanism linking serum GGT to CHD among general population. Even though the strength of association appeared to be modest among all subjects, stronger associations were observed among subjects aged <60 and among alcohol drinkers. Especially, measurement of serum GGT among type-2 diabetics may be helpful to predict the future risk of CHD.

Adult↗

PubMed2006

How well does the metabolic syndrome defined by five definitions predict incident diabetes and incident coronary heart disease in a Chinese population?

We evaluate the ability of the metabolic syndrome (MetS) defined by five definitions for predicting both incident CHD and diabetes combined, diabetes alone, and CHD alone in a Chinese population. The screening survey for type 2 diabetes was conducted in 1994. A follow-up study of 541 high-risk non-diabetic individuals who were free of CHD at baseline was carried out in 1999 in Beijing area. The MetS was defined by the World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), American College of Endocrinology (ACE), the International Diabetes Federation (IDF), and the National Cholesterol Education Program and the American Heart Association (AHA) (updated NCEP) criteria. From a multiple logistic regression adjusting for age, sex, education, occupation, smoking, family history of diabetes, and total cholesterol, the relative risk of the ACE-defined MetS for incident diabetes alone (67 cases) was 2.29 (95% CI, 1.20-4.34). The MetS defined by the five definitions was associated with a 1.8-3.9 times increased risk for both incident CHD and diabetes combined (59 cases), and with a 1.9-3.0 times for total incident diabetes (126 cases). None of the five definitions predicted either incident CHD alone (177 cases) or total incident CHD (236 cases). In conclusion, the MetS defined by the current definitions appears to be more effective at predicting incident diabetes.

Adult↗

PubMed2006

Sporadic feedback control of flow turbulence.

In this work we consider the problem of flow turbulence control in a two-dimensional Navier-Stokes equation. We suggest a control strategy which sporadically applies global feedback to a single velocity component of the velocity field. It is found that this control strategy can significantly enhance the control efficiency when the optimal fraction for the control period is suitably chosen, both larger and smaller control time fractions may reduce the control precision. The physical mechanism underlying this interesting and strange behavior is heuristically analyzed, based on mode-mode interactions.

Journal Article↗

PubMed2006

Controlling drift-wave turbulence using time-delay and space-shift autosynchronization feedback.

Drift-wave turbulence control in a one-dimensional nonlinear drift-wave equation driven by a sinusoidal wave is considered. We apply time-delay and space-shift feedback signals, to suppress turbulence. By using global and local pinning strategies, we show numerically that the turbulent state can be controlled to periodic states effectively if appropriate time-delay length and space-shift distance are chosen. The physical mechanism of the control scheme is understood based on the energy-minimum principle.

Journal Article↗

PubMed2006

Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and glutamate levels in the nucleus accumbens of rats.

Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been reported that Ipt inhibited cocaine-induced dopamine and glutamate release, suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a heterologously expressed SH-EP1 cell line and in native midbrain dopamine neurons. In the present study, we examined whether Ipt prevents nicotine-induced neurotransmitter release in the nucleus accumbens (NAc) using in vivo microdialysis methods in awake, freely moving rats. Ipt was administered through a microdialysis probe, following systemic administration of nicotine (0.5 mg/kg, s.c.). The results show that acute nicotine treatment induced an increase of both dopamine and glutamate levels in the rat NAc, and that Ipt significantly attenuated nicotine's effects in a concentration-dependent manner. Therefore, Ipt may serve as a novel compound to block nicotine-induced dopamine and glutamate release in the brain reward center, in turn decreasing nicotine reinforcement and dependence.

Analysis of Variance↗