RhoGDIβ-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK

We found that overexpression of RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and suppressed cell cycle progression in a cultured cardiomyoblast cell line. Knockdown of RhoGDIβ expression by RNA interference blocked hypertrophic growth. We further demonstrated that RhoGDIβ physically interacts with ZAK and is phosphorylated by ZAK in vitro, and this phosphorylation negatively regulates RhoGDIβ functions. Moreover, the ZAK-RhoGDIβ interaction may maintain ZAK in an inactive hypophosphorylated form. These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIβ functions through phosphorylation and RhoGDIβ counteracts the effects of ZAK by physical interaction. Knockdown of ZAK expression in ZAK- and RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the full functions of RhoGDIβ

ZAK negatively regulates RhoGDIβ-induced Rac1-mediated hypertrophic growth and cell migration

RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIβ plays a previously undefined role in regulating Rac1 expression through transcription to induce hypertrophic growth and cell migration and that these functions are blocked by the expression of a dominant-negative form of Rac1. We also demonstrated that knockdown of RhoGDIβ expression by RNA interference blocked RhoGDIβ-induced Rac1 expression and cell migration. We demonstrated that the co-expression of ZAK and RhoGDIβ in cells resulted in an inhibition in the activity of ZAK to induce ANF expression. Knockdown of ZAK expression in ZAK-RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the activities of RhoGDIβ

Up-regulation of the expression of cocaine and amphetamine-regulated transcript peptide by electroacupuncture in the arcuate nucleus of diet-induced obese rats

Abstract It was reported that acupuncture or electro-acupuncture (EA) is effective in reducing the body weight for obese patients, although the mechanisms remain obscure. In a previous study, we have found that rats fed with high-fat (HIF) diet developed diet-induced obesity (DIO) with a concomitant decrease in the hypothalamic content of the cocaine and amphetamine-regulated transcript (CART) peptide, a peptide with anorexiogenic effect. To assess the central effect of EA on DIO rat, we revealed that EA up-regulated the expression of CART peptide in the arcuate nucleus (ARC) of the DIO rats. After feeding with HIF diet for 14 weeks, the DIO rats received EA stimulation three times per week for 4 weeks. The expression of CART peptide in ARC was measured using immunohistochemistry. The plasma ACTH was measured with ELISA. EA caused a reduction of both body weight and energy intake in DIO rats and increased the expression of CART peptide in ARC. The plasma ACTH was increased in response to restraint stress, but EA produced no further increase in ACTH levels. The results suggest that EA can up-regulate the expression of CART peptide to approach normal level, resulting in an inhibition of food intake and a reduction of body weight in DIO rats. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Electroacupuncture; CART; Body weight; Diet-induced obesity; Arcuate nucleus In humans and animals, a chronic high-fat (HIF) diet without a compensatory increase in energy expenditure leads to the progressive development of obesity E-mail addresses: [email protected], [email protected] (J.-S. Han). 1 Present address: Department of Surgery, Tianjin No. 3 Central Hospital, Tianjin 300170, China. tiveness of acupuncture, and even today, it is not generally regarded as scientifically acceptable. The problem has always been the difficulty to explain the mechanisms behind the effects of acupuncture, and to demonstrate its effects in controlled clinical trials As in much of human obese cases, the rat model of dietinduced obesity (DIO) appears to follow a polygenic mode in inheritance. Hypothalamic neuropeptides play an important role in regulating energy balanc

Phosphorylation ofserine-504oftNOX(ENOX2)modulates cell proliferationandmigrationincancercells

Tumor-associatedNADHoxidase(tNOX;ENOX2)isagrowth-relatedproteinexpressedin transformed cells.Consistentwiththisfunction,tNOXknockdownbyRNAinterferenceleadsto a significantreductionincellproliferationandmigrationinHeLacells,whereastNOX overexpression confersanaggressivephenotype.Here,forthefirsttime,wereportthattNOX is phosphorylatedbyproteinkinaseCd (PKCd) both in vitro and in vivo. Replacementofserine- 504 withalaninesignificantlyreducesphosphorylationbyPKCd. Co-immunoprecipitation experiments revealaninteractionbetweentNOXandPKCd. Moreover,whereasoverexpression of wild-typetNOXinNIH3T3cellsincreasescellproliferationandmigration,overexpressionof the S504AtNOXmutantleadstodiminishedcellproliferationandmigration,reflectingreduced stability oftheunphosphorylatabletNOXmutantprotein.Collectively,theseresultssuggestthat phosphorylationofserine-504byPKCd modulates thebiologicalfunctionoftNOX

Increased Risk of Ischemic Stroke in Patients with Benign Paroxysmal Positional Vertigo: A 9-Year Follow-Up Nationwide Population Study in Taiwan

Benign paroxysmal positional vertigo (BPPV) is a common form of vertigo and is characterized by episodic dizziness related to changes in head position relative to gravity. Benign paroxysmal positional vertigo symptoms can be similar to those of central nervous system vascular diseases. The association between BPPV and ischemic stroke has not yet been investigated. The study cohort consisted of patients who were diagnosed with BPPV at least twice in the previous year as an outpatient or for whom BPPV was the primary diagnosis as an inpatient (n = 4104). An age- and gender-matched sample that excluded patients with a diagnosis of any form of vertigo was selected as the comparison cohort (n = 8397). All cases were followed up from January 1, 2000, to December 31, 2008. The demographic characteristics, medical comorbidities and use of medications in both groups were investigated using chi-square tests. A stratified analysis of stroke risk factors was performed to determine the hazard ratios of BPPV. During the 9-year follow-up period, 185 of the 4104 (4.5%) subjects with BPPV and 240 of the 8379 (2.9%) subjects without BPPV developed ischemic strokes. The crude hazard ratio of BPPV for developing ischemic strokes was 1.708. After adjusting for stroke risk factors, the risk of developing ischemic strokes in BPPV subjects was 1.415-fold higher than the risk among those without BPPV (confidence interval: 1.162-1.732, p = 0.001). After a subgroup analysis stratified according to stroke risk factors, BPPV remained independently associated with a higher risk of developing future ischemic stroke. We conclude that BPPV is independently associated with a risk of subsequent ischemic stroke. More aggressive control of modifiable risk factors for ischemic strokes should be conducted in patients with BPPV