Ying-Ming Liou

MPTP Lesion Causes Neuroinflammation and Deficits in Object Recognition in Wistar Rats

Animal models of Parkinsons disease with dementia would greatly facilitate research into the underlying causes of this disorder. Here, we showed that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, cell loss in the hippocampal CA1 area, as well as microglial activation and increase of interleukin-2 levels in several brain regions. In addition, increase of anxiety-like behavior and impairment of object recognition were observed in the MPTP-lesioned rats. These findings suggest that neuroinflammation may contribute to MPTP-induced neurodegeneration and behavioral deficits, which is suggested as an animal model of Parkinsons disease dementia.

MPTP-induced dopaminergic degeneration and deficits in object recognition in rats are accompanied by neuroinflammation in the hippocampus

Emotional changes, impairment of object recognition, and neuroinflammation are seen in Parkinsons disease with dementia (PDD). Here, we show that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the rat substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, microglial activation in the SNc and hippocampus, and cell loss in the hippocampal CA1 area. With regard to behavior, an increase in anxiety-like behavior and impairment of object recognition were observed during the fourth week after MPTP lesioning. The behavioral changes were not caused by motor impairment, since the rats had already recovered from MPTP-induced catalepsy before the tests were performed. These findings show that MPTP-induced neuroinflammation and its consequences, for example, microglial activation and cell loss in the hippocampus, may be involved in dopaminergic degeneration-related behavioral deficits and suggest that, in addition to the dopaminergic system, the limbic system may also participate in the pathophysiology of PDD. MPTP-lesioned rats are therefore proposed as a useful tool for assessing the ability of pharmacological agents to prevent recognition deficits in PDD.

The anti-cancer effects of (−)-Epigalocathine-3-gallate on the signaling pathways associated with membrane receptors in MCF-7 cells

(−)‐Epigallocatechin‐3‐gallate (EGCg) has been implicated in cancer chemo‐prevention in studies using many different kinds of cancer cells. The present study measured cell viability, osteopontin (OPN) secretion, fatty acid synthase (FAS) expression, and cytosolic Ca2+ and verified the anti‐cancer activities of EGCg in MCF‐7 human breast cancer cells. EGCg‐induced apoptosis was evidenced by nuclear condensation, increased protein levels of activated caspase‐3, down‐regulation of gelsolin and tropomyosin‐4 (Tm‐4), and up‐regulation of tropomyosin‐1(Tm‐1). By disrupting adherens junction formation, EGCg caused accumulation of extra‐nuclear β‐catenin aggregates in the cytosol and alterations of the protein content and mRNA expression of E‐cadherin and β‐catenin, but not N‐cadherin, in MCF‐7 cells. To identify the putative mechanisms underlying the EGCg signaling pathways, EGFP (enhanced green fluorescence protein) was ectopically expressed in MCF‐7 cells. This allowed us to monitor the EGCg‐induced fluorescence changes associated with the effects of Triton X‐100 (to remove plasma membrane) or the addition of laminin, anti‐laminin receptor (LR) antibody, epidermal growth factor (EGF), and genistein on the cells. Our results indicated that EGCg acts via the signaling pathways associated with cell membrane to suppress cell proliferation, provoke apoptosis, and disturb cell–cell adhesion in MCF‐7 cells. The altered events include the EGFR, LR, FAS, intracellular Ca2+, OPN secretion, caspace‐3, gelsolin, Tm‐4, Tm‐1, and adherens junction proteins, E‐cadherin and β‐catenin. J. Cell. Physiol. 226: 2721–2730, 2011.

Molecular targets for anti-oxidative protection of green tea polyphenols against myocardial ischemic injury

Ischemic heart disease is the leading cause of death worldwide. An improved understanding of the mechanisms involved in myocardial injury would allow intervention downstream in the pathway where certain drugs including natural products could be efficiently applied to target the end effectors of the cell death pathway. Green tea polyphenols (GTPs) have potent anti-oxidative capabilities, which may account for their beneficial effects in preventing oxidative stress associated with ischemia injury. Although studies have provided convincing evidence to support the protective effects of GTPs in cardiovascular system, the potential end effectors that mediate cardiac protection are only beginning to be addressed. Proteomics analyses widely used to identify the protein targets for many cardiovascular diseases have advanced the discovery of the signaling mechanism for GTPs-mediated cardio-protection. This review focuses on putative triggers, mediators, and end effectors for the GTPs-mediated cardio-protection signaling pathways engaged in myocardial ischemia crisis, allowing a promising natural product to be used for ameliorating oxidative stress associated with ischemic heart diseases.

The Role of False Lumen Size in Prediction of In-Hospital Complications After Acute Type B Aortic Dissection

OBJECTIVES The aim of this study was to determine whether false lumen size predicts in-hospital complications for acute type B aortic dissection. BACKGROUND The incidence of complications developing in patients with acute type B aortic dissection has been high. However, methods for recognizing high-risk patients have not been well-studied. We used quantitative analysis by computed tomography (CT) to predict the occurrence of in-hospital complications. METHODS Fifty-five consecutive patients with acute type B aortic dissection documented by CT imaging were analyzed. They were divided into groups, with and without in-hospital complications, and compared regarding maximal aortic diameter (MAD), maximal false lumen area (MFLA), minimal true lumen area (MTLA), branch-vessel involvement (BVI), and longitudinal length (LL) of aortic dissection. RESULTS There were 31 patients with a stable course (group 1) and 24 patients who developed complications (group 2). The MFLA of group 2 was significantly larger than that of group 1 (group 1 vs. group 2=577.7+/-273.2 mm2 vs. 1,899.3+/-1,642.4 mm2, p<0.001). The BVI number was also higher in group 2 (group 1 vs. group 2=1.0+/-1.1 vs. 3.3+/-2.0, p<0.001). On multivariate analysis, only MFLA and BVI number were independent predictors of in-hospital complications. Patients with initial MFLA>or=922 mm2 or BVI number>or=2 showed a significantly higher incidence of in-hospital complications than the other patients (p<0.001). CONCLUSIONS A large MFLA and a higher BVI number are powerful predictors of in-hospital complications after acute type B aortic dissection.

Effects of Genistein on β-Catenin Signaling and Subcellular Distribution of Actin-Binding Proteins in Human Umbilical CD105-Positive Stromal Cells

This study was performed to define the roles of actin‐binding proteins in the regulation of actin filament assembly associated with cellular signal transduction pathways in stromal cell proliferation. Genistein, a tyrosine protein kinase inhibitor, decreased the intracellular Ca2+ and attenuated cell proliferation and DNA synthesis through the β‐catenin and cyclin D1 pathway in human umbilical CD105‐positive cells. Immunoprecipitation studies using anti‐β‐actin antibody revealed that several actin‐binding proteins implicated in cells include formin‐2 (FMN‐2), caldesmon (CaD), tropomyosin (Tm), and profilin. Protein levels of these proteins in whole cell lysates were not significantly changed by genistein. Three Tm isoforms, Tm‐1, Tm‐2, and Tm‐4, were found to be present in cells. Genistein caused a reduction in levels of mRNAs coding for Tm‐1 and Tm‐4, but had no significant effect on Tm‐2 mRNA levels. Immunofluorescence confocal scanning microscopy indicated that changes in the subcellular distribution of Tm and CaD, in which the diffuse cytosolic staining was shifted to show colocalization with actin stress fibers. In contrast, genistein‐induced accumulation of FMN‐2 and profilin in the peri‐nuclear area. Silencing of FMN‐2 by small interfering RNA resulted in increases of intracellular Ca2+ and rendered genistein resistance in decreasing intracellular Ca2+ in cells. These results provide the novel findings that genistein acts by modulating the cellular distribution of actin‐binding proteins in association with alterations of cellular signal transduction pathways in human stromal cell proliferation. J. Cell. Physiol. 223: 423–434, 2010.

Early development in Williams syndrome.

Background: The aim of the present study was to gain a better understanding of the motor performance in Williams syndrome for early intervention of rehabilitation programs.

Electroacupuncture-induced pressor and chronotropic effects in anesthetized rats

The effects of electroacupuncture (Ea) on circulatory dynamics were investigated in anesthetized rats. The arterial blood pressure (BP) and the heart rate (HR) in response to Ea stimulations at the Tsusanli point (St-36) and the Hoku point (Li-4) were tested by a low frequency Ea (2 Hz; LFEa) and a high frequency Ea (20 Hz; HFEa) with stimulation intensities 20 times the motor threshold. Neither the HR nor the BP was affected when the Tsusanli point was stimulated. Whereas, Ea stimulations at the Hoku point elicit chronotropic and pressor effects. The patterns of pressor responses caused by the LFEa were different from that of an HFEa, i.e., the LFEa elicited a tonic effect, while an HFEa had a phasic one. The HFEa-induced pressor and chronotropic effects were attenuated, while the LFEa induced effects were completely blocked by an intravenous infusion of an alpha-adrenergic blocker (moxisylyte 0.2 mg/min/kg, i.v., for 20 min). A co-infusion with alpha-and beta-adrenergic blockers (propanolol 0.2 mg/min/kg, i.v., for 20 min) completely blocked the HFEa-induced pressor and chronotropic effects. We concluded that Ea stimulations, at the Hoku acupoint, with appropriate stimulation parameters can increase and maintain BP. Furthermore, the LFEa stimulation activates sympathetic vasomotor tone, whereas the HFEa stimulation causes an additional potentiation on the sympathetic drive to the heart.

Regulatory mechanism of smooth muscle contraction studied with gelsolin-treated strips of taenia caeci in guinea pig

The potential roles of the regulatory proteins actin, tropomyosin (Tm), and caldesmon (CaD), i.e., the components of the thin filament, in smooth muscle have been extensively studied in several types of smooth muscles. However, controversy remains on the putative physiological significance of these proteins. In this study, we intended to determine the functional roles of Tm and CaD in the regulation of smooth muscle contraction by using a reconstitution system of the thin filaments. At appropriate conditions, the thin (actin) filaments within skinned smooth muscle strips of taenia caeci in guinea pigs could be selectively removed by an actin-severing protein, gelsolin, without irreversible damage to the contractile apparatus, and then the thin filaments were reconstituted with purified components of thin filaments, i.e., actin, Tm, and CaD. We found that the structural remodeling of actin filaments or thin filaments was functionally linked to the Ca(2+)-induced force development and reduction in muscle cross-sectional area (CSA). That is, after the reconstitution of the gelsolin-treated skinned smooth muscle strips with pure actin, the Ca(2+)-dependent force development was partially restored, but the Ca(2+)-induced reduction in CSA occurred once. In contrast, the reconstitution with actin, followed by Tm and CaD, restored not only the force generation but also both its Ca(2+) sensitivity and the reversible Ca(2+)-dependent reduction in CSA. We confirmed that both removal of the thin filaments by gelsolin treatment and reconstitution of the actin (thin) filaments with Tm and CaD caused no significant changes in the level of myosin regulatory light chain phosphorylation. We thus conclude that Tm and CaD are necessary for the full regulation of smooth muscle contraction in addition to the other regulatory systems, including the myosin-linked one.

Pressor effects on blood pressure induced by isovolumic bladder distension and electro-acupuncture stimulations in anesthetized rats.

The pressor effects on blood pressure (BP) elicited by electro-acupuncture (Ea) stimulations and vesico-vascular reflex (VVR) were investigated in anesthetized rats. Twenty adult female Sprague-Dawley rats were used throughout this study. Two acupoints, the Hoku (Li-4) and the Tsusanli (St-36), were tested by a low frequency Ea (LFEa, 2 Hz) and a high frequency Ea (HFEa, 20 Hz) with intensities 20 times that of the motor threshold. Ea at Tsusanli elicited no pressor effects (98.15 +/- 4.10% and 101.43 +/- 3.96% of pre-stimulation control in LFEa and HFEa, respectively) whereas pressor effects could be induced by Ea stimulations at Hoku (126.3 +/- 3.3% and 136.3 +/- 3.8% of pre-stimulation control in LFEa and HFEa, respectively, P < 0.01, n=10). In addition, the patterns of pressor effects elicited by LFEa and HFEa at Hoku were different, i.e., LFEa at Hoku elicited a tonic pressor effect, while HFEa elicited a phasic one. The VVR induced by bladder isovolumic saline distension also elicited a pressor effect on BP (119.2 +/- 2.2%, P < 0.01, n=10) in the same preparations during bladder contractions. The VVR did not modify the Ea-induced pressor responses, and vice versa, when both of them were superimposed. All the results suggested that the pressor effects elicited by the VVR and the Ea stimulation were additive responses. In addition, for future clinical application, our findings may imply that patients should be carefully monitored for signs and symptoms of autonomic dysfunction during clinical acupuncture treatments.