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Osamu Yokoyama

Publications and source records attributed to Osamu Yokoyama.

At least 19 recordsLinked to original sources
PubMed2007

Identification of alpha-1L and alpha-1A adrenoceptors in human prostate by tissue segment binding.

PURPOSE: Silodosin (KMD-3213 or [(-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide]) (Kissei Pharmaceutical Co., Ltd., Matsumoto, Japan) is a selective antagonist for alpha-1A and alpha-1L adrenoceptors. Using this tritiated ligand the 2 alpha-1 adrenoceptors were examined in binding studies with intact tissue segments and membrane preparations of human prostate, and compared with functionally identified alpha-1 adrenoceptor. MATERIALS AND METHODS: Binding assays with tissue segments and membrane preparations of human prostate samples were performed using [3H]-silodosin and binding affinities for various drugs were estimated. In functional experiments antagonist affinities were evaluated from the inhibitory potency against the contractile response to noradrenaline. RESULTS: [3H]-silodosin bound to intact segments and membrane preparations of human prostate with subnanomolar affinity. [3H]-silodosin binding sites in intact segments were divided into 2 distinct components with different affinities for prazosin and RS-17053 (N-[2(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl1H-indole-3-ethanamine hydrochloride) (Research Biochemicals International, Natick, Massachusetts), while binding in membrane preparations showed single high affinity for these drugs. [3H]-silodosin binding sites also showed high affinity for silodosin and tamsulosin but low sensitivity to BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione) (Research Biochemicals International) in intact segments and in membrane preparations. In functional experiments silodosin and tamsulosin potently inhibited the contractile response to noradrenaline but prazosin, RS-17053 and BMY 7378 showed low antagonistic affinity. CONCLUSIONS: The current binding studies in human prostate samples clearly show that alpha-1L and alpha-1A adrenoceptors coexist as pharmacologically distinct entities in intact tissues but not in crude membrane preparations. Also, alpha-1 adrenoceptors involved in the contractile response to noradrenaline are the alpha-1L subtype.

Humans↗
PubMed2007

Improvement in bladder storage function by tamsulosin depends on suppression of C-fiber urethral afferent activity in rats.

PURPOSE: Alpha(1)-blockers improve voiding symptoms by decreasing prostatic and urethral smooth muscle tone. However, to our knowledge the mechanism underlying improvements in storage symptoms is not known. Topical application of prostaglandin E(2) to the rat lower urinary tract stimulates the micturition reflex. Using an animal model we investigated whether the alpha(1)-blocker tamsulosin (Astellas Pharma, Tokyo, Japan) acts on C-fiber afferent activity and, if so, the location of this effect. MATERIALS AND METHODS: To induce desensitization of C-fiber afferent activity resiniferatoxin (0.3 mg/kg) was subcutaneously injected in female Sprague-Dawley rats 2 days before experiments. Simultaneous recordings of urethral pressure and rhythmic bladder pressure were made with the rats under urethane anesthesia. Prostaglandin E(2) (0.4 mg/ml) was continuously administered intravesically or intraurethrally to rats pretreated with resiniferatoxin (resiniferatoxin rats) or rats without pretreatment (nonresiniferatoxin rats). We investigated the effects on the micturition reflex of intravenous (2.2 x 10(-1) to 2.2 x 10(3) nM/kg) or intrathecal (0.001 to 0.1 nmol) administration of tamsulosin. RESULTS: The bladder contraction interval was markedly decreased after intravesical or intraurethral administration of prostaglandin E(2) in nonresiniferatoxin rats but it was unchanged in resiniferatoxin rats. This effect was antagonized by the EP1 receptor antagonist ONO-8711 (6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]-5Z-hexenoic acid). Intravenous administration of tamsulosin significantly increased the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2) but it had no effect on nonresiniferatoxin rats receiving intravesical prostaglandin E(2). Intrathecal administration of tamsulosin produced a slight and insignificant increase in the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2). CONCLUSIONS: These results suggest that prostaglandin E(2) enhances the micturition reflex through C-fiber afferents and tamsulosin had an inhibitory effect on the C-fiber urethral afferent nerves, thereby improving bladder storage function.

Adrenergic alpha-Antagonists↗
PubMed2006

Tactile stimulation-induced rapid elevation of the synaptophysin mRNA expression level in rat somatosensory cortex.

Synaptophysin is an integral membrane protein abundant in the synaptic vesicle and is found in nerve terminals throughout the brain. It was recently suggested that synaptophysin is also involved in the modulation of activity-dependent synapse formation. In this study, we examined at the individual level whether tactile stimulation selectively influenced the synaptophysin mRNA expression level in the somatosensory cortex of rats. Anesthetized rats were caressed on the back by an experimenter's palms for 20 min and the mRNA expression levels in the somatosensory and the visual cortices 5 min afterwards were determined using quantitative PCR methodology. The synaptophysin mRNA expression level was selectively higher in the experimental group than in the control group in the somatosensory cortex but not in the visual cortex. This suggests that the mRNA expression level of synaptophysin induced by neuronal activity is related to the regulation of synapse formation or remodeling or both.

Animals↗
PubMed2006

Improvement of bladder storage function by alpha1-blocker depends on the suppression of C-fiber afferent activity in rats.

AIMS: Alpha1-blockers improve voiding symptoms through the reduction of prostatic and urethral smooth muscle tone; however, the underlying mechanism of improvement of storage symptoms is not known. Using a rat model of detrusor overactivity caused by cerebral infarction (CI), we undertook the present study to determine whether the effect of an alpha1-blocker, naftopidil, is dependent on the suppression of C-fiber afferents. METHODS: To induce desensitization of C-fiber bladder afferents, we injected resiniferatoxin (0.3 mg/kg, RTX) sub-cutaneously to female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO) (RTX-CI rats). As controls we used rats without RTX treatment (CI rats). MCAO and insertion of a polyethylene catheter through the bladder dome were performed under halothane anesthesia. We investigated the effects on cystometrography (CMG) of intravenous (i.v.), intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of naftopidil in conscious CI rats. RESULTS: Bladder capacity (BC) was markedly reduced after MCAO in both RTX-CI and CI rats. I.v. administration of naftopidil significantly increased BC in CI rats without an increase in residual volume, but it had no effects on BC in RTX-CI rats. I.t. administration of naftopidil significantly increased BC in CI but not in RTX-CI rats. CONCLUSIONS: These results suggest that naftopidil has an inhibitory effect on C-fiber afferents in the lumbosacral spinal cord, improving BC during the storage phase.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2006

Paraplegia after aortic aneurysm repair versus traumatic spinal cord injury: functional outcome, complications, and therapy intensity of inpatient rehabilitation.

OBJECTIVE: To compare outcomes, complications, and therapy intensity of inpatient rehabilitation in patients with paraplegia caused by spinal cord injury associated with aortic aneurysm repair (SCI-AA) versus patients with traumatic spinal cord injury (SCI). DESIGN: Case-controlled study. SETTING: SCI unit in a rehabilitation center. PARTICIPANTS: Seventeen patients with SCI-AA and 17 patients with traumatic SCI. INTERVENTION: Standard rehabilitation therapy for SCI. MAIN OUTCOME MEASURES: Length of stay (LOS) in acute and rehabilitation hospitals; FIM instrument scores; FIM change; FIM efficiency; complications; therapy intensity; and ambulatory state and return to community at discharge. RESULTS: No significant differences were noted in acute and rehabilitation LOS and admission FIM scores. Discharge FIM scores, FIM change, and FIM efficiencies were significantly lower in the SCI-AA group, which had many complications related to AA and SCI. Intensity of rehabilitation sports therapy in the SCI-AA group was significantly lower than that of the traumatic SCI group, but total therapy intensity did not differ significantly. Both had similar rates of return to ambulatory state and discharge to the community. CONCLUSIONS: SCI-AA patients had many complications that interfered with rehabilitation therapy, and could not achieve functional gains comparable to those with traumatic SCI. However, both groups achieved comparable success with return to ambulatory state and discharge to the community.

Adult↗
PubMed2006

A selective alpha1A-adrenoceptor antagonist inhibits detrusor overactivity in a rat model of benign prostatic hyperplasia.

PURPOSE: Alpha(1)-adrenoceptor antagonists relax the obstructed prostatic urethra and suppress the irritative symptoms frequently observed in patients with benign prostatic hyperplasia. We investigated the effects of 3 alpha(1)-adrenoceptor antagonists on urodynamics in rats with hormone induced benign prostatic hyperplasia to determine which alpha(1)-adrenoceptor subtype selective antagonists would suppress irritative symptoms. MATERIALS AND METHODS: Rats were treated with testosterone and 17beta-estradiol by weekly intramuscular injections. After 4 weeks a pressure flow study was done and the effects of the alpha(1)-adrenoceptor antagonists KMD-3213 silodosin, tamsulosin and prazosin on urodynamics were compared. We especially investigated the involvement of the bladder and prostatic urethra to clarify the mechanism of detrusor overactivity expression. RESULTS: Hormone treatment induced benign prostatic hyperplasia and resulted in detrusor overactivity, as determined by cystometry. Baseline perfusion urethral pressure and the phenylephrine induced increase in it were significantly higher in rats with vs without benign prostatic hyperplasia. Cystometry in hormone treated female rats did not show detrusor overactivity. KMD-3213 decreased detrusor overactivity, similar to other alpha(1)-adrenoceptor antagonists. CONCLUSIONS: These results suggest that an excessive response to sympathetic nerve stimulation, which is mainly mediated via alpha(1A)-adrenoceptor, in the hypertrophied prostate gives rise to detrusor overactivity. Furthermore, the alpha(1A)-adrenoceptor selective antagonist KMD-3213 would be suitable for improving irritative symptoms in patients with benign prostatic hyperplasia.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2006

Symptom assessment tool for overactive bladder syndrome--overactive bladder symptom score.

OBJECTIVES: Overactive bladder (OAB) is a common symptom syndrome with urgency, urinary frequency, and urgency incontinence. To collectively express OAB symptoms, we developed the overactive bladder symptom score (OABSS). METHODS: Four symptoms--daytime frequency, nighttime frequency, urgency, and urgency incontinence--were scored. The weighing score was based on a secondary analysis of an epidemiologic database. Psychometric properties were examined in five patient groups: OAB (n = 83), asymptomatic controls (n = 34), stress incontinence (n = 29), benign prostatic hyperplasia (n = 28), and other diseases with urinary symptoms (n = 26). RESULTS: The maximal score was defined as 2, 3, 5, and 5 for daytime frequency, nighttime frequency, urgency, and urgency incontinence, respectively. The sum score (OABSS 0 to 15) was significantly greater in the patients with OAB (8.36) than in the other patient groups (1.82 to 5.14). The distribution of the OABSS showed a clear separation between those with OAB and asymptomatic controls. The OABSS correlated positively with the individual scores (Spearman's r = 0.10 to 0.78) and quality-of-life scores assessed by the King's Health Questionnaire (Spearman's r = 0.20 to 0.49). The weighted kappa coefficients were 0.804 to 1.0 for each symptom score and 0.861 for OABSS. The posttreatment reduction in the OABSS was consistent with the global impression of patients of the therapeutic efficacy. CONCLUSIONS: The OABSS, the sum score of four symptoms (daytime frequency, nighttime frequency, urgency, and urgency incontinence), has been developed and validated. OABSS may be a useful tool for research and clinical practice.

Aged↗
PubMed2006

Endovascular treatment for an iliac artery-ureteral fistula with a covered stent.

Iliac artery-ureteral fistula (IAUF) is a rare entity that has a potential risk of life-threatening hemorrhage. It is difficult to diagnose and treat appropriately. Conventional treatment for the disease consists of surgical ligation and vascular reconstruction or coil embolization. Surgical treatment is usually difficult for patients with several risk factors. In recent years, endovascular stent-graft treatment for iliac artery pseudoaneurysm has been reported. The present report describes two cases in which endovascular covered stent-graft treatment was successfully applied to treat IAUF, with good clinical outcomes.

Aged↗
PubMed2006

Correlation between the Aging Males' Symptoms Scale and sex steroids, gonadotropins, dehydroepiandrosterone sulfate, and growth hormone levels in ambulatory men.

INTRODUCTION: Partial androgen deficiency of the aging male (PADAM) is defined as a biochemical syndrome associated with advancing age that is characterized by a deficiency in serum androgen levels. The Aging Males' Symptoms (AMS) Scale was developed to evaluate PADAM-related symptoms and is currently used worldwide; however, it has been reported that PADAM-related symptoms evaluated by this scale are not related to serum testosterone levels. In addition to testosterone, the levels of other hormones also decrease with age; therefore, multihormone alterations may influence PADAM-related symptoms. AIM: To investigate the relationship between PADAM-related symptoms evaluated by the AMS Scale and serum levels of testosterone, estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEA-S), and growth hormone (GH) in men. METHODS: A total of 141 ambulatory men were recruited after excluding men with endocrine and other related diseases. All participants completed the AMS questionnaire and an analysis of serum levels of total and free testosterone (TT and FT), E2, LH, FSH, DHEA-S, and GH. MAIN OUTCOME MEASURE: The relationship between AMS scores (total and subscores) and serum hormone levels was determined. RESULTS: There were significant negative correlations between age and serum FT and DHEA-S levels, as well as positive correlations between age and serum LH and FSH levels, but no correlation between age and AMS scores. None of the three AMS domain scale scores and total scores significantly correlated with serum levels of TT, FT, E2, LH, FSH, DHEA-S, or GH. CONCLUSIONS: The results of the present study suggest that PADAM-related symptoms as evaluated by the AMS Scale are not significantly related to serum levels of TT, FT, E2, LH, FSH, DHEA-S, or GH. Because many factors related to aging are thought to contribute to the occurrence of PADAM-related symptoms, the AMS Scale may not be able to predict serum hormone levels.

Adult↗
PubMed2006

A case of bilateral testicular calcifications in a bicycle motocross rider accompanied by bulbar urethral injury.

A 21-year-old Japanese man who was a professional bicycle motocross rider injured his perineum during a competition. Chief complaints were gross hematuria, perineal pain, and subcutaneous ecchymosis of the scrotum. Urethrocystography revealed a torn bulbar urethra and extravasation in the same region. Scrotal ultrasonography revealed small calcifications in the bilateral testes. Here, we report a case of bilateral testicular calcifications caused by the continuous shock and vibration of the saddle in an off-road bicycle rider.

Adult↗
PubMed2005

Kinematic effects on gait of a newly designed ankle-foot orthosis with oil damper resistance: a case series of 2 patients with hemiplegia.

The ankle joint of ankle-foot orthoses (AFOs) should restrict plantarflexion to prevent foot drop during the swing phase. However, excessive plantarflexion resistance causes excessive knee flexion during the stance phase. Plantarflexion resistive moment should be easily adjustable according to the gait ability of patients with hemiplegia. Because it is difficult to adjust plantarflexion resistive moment exactly, we developed an AFO with an oil damper. It is a small shock absorber that utilizes hydraulic resistance. The oil damper generates a resistive moment to the plantarflexion rotation of the ankle joint at the initial stance phase. The magnitude of the plantarflexion resistive moment at the heel strike can be easily adjusted to accommodate each patient's condition by simply turning an adjustment screw. We used a gait analysis system to compare the gait of 2 hemiplegic patients while they were wearing either the AFO with the oil damper or the AFO with the plantarflexion stop. The AFO with the oil damper achieved sufficient plantarflexion of the ankle and mild flexion of the knee by adjusting a proper plantarflexion resistive moment during initial stance phase, and provided a more comfortable gait than did the AFOs with a plantarflexion stop.

Ankle↗
PubMed2005

Role of cyclooxygenase-2 in the development of bladder overactivity after cerebral infarction in the rat.

PURPOSE: We investigated the role of cyclooxygenase (COX) isoforms in bladder overactivity induced by cerebral infarction (CI) in rats. MATERIALS AND METHODS: CI was induced by left middle cerebral artery occlusion (MCAO) in female Sprague-Dawley rats. Bladder activity was monitored with continuous infusion cystometrography of conscious rats. Specimens were obtained from the pontine tegmental area (PTA) 1, 3, 5, 12 and 24 hours after CI or sham operation (SO). The effects of MK-801 (0.1 mg/kg intravenously), an NMDA (N-methyl-D-aspartate) glutamatergic receptor antagonist, on bladder activity, and on COX-1 and 2 mRNA expression following MCAO were examined. Real-time quantitative reverse transcriptase-polymerase chain reaction was performed to evaluate the effects of CI on gene expression in the PTA. The effects of the COX-2 inhibitor NS398 (0.01 to 10 mg/kg intravenously) on bladder activity were examined. RESULTS: The bladder capacity of CI rats was significantly decreased 1 to 24 hours after MCAO compared with that of SO rats (p <0.05 or 0.01). One and 3 hours after MCAO mean COX-2 mRNA expression +/- SE had increased significantly to 22.4 +/- 3.5 in terms of its expression relative to the outer control in a sample obtained immediately after MCAO, in contrast to that in SO rats (p <0.01). The expression level returned to the control level within 12 hours after MCAO. COX-1 expression was not influenced by MCAO. Pretreatment with MK-801 inhibited the development of bladder overactivity and significantly decreased the expression of COX-2 mRNA in the PTA (p <0.01). Treatment with NS398 before MCAO prevented the development of bladder overactivity in a dose dependent manner and did not influence infarct volume. CONCLUSIONS: These results indicate that the development of bladder overactivity following MCAO is accompanied by an increase in COX-2 mRNA expression in the PTA and is mediated by NMDA receptor activity. COX-2 in the brain may be a new target for the treatment of neurogenic voiding dysfunction after cerebral infarction.

Animals↗
PubMed2005

Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats.

PURPOSE: We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically. MATERIALS AND METHODS: To induce C-fiber bladder afferent nerve desensitization resiniferatoxin (RTX) (0.3 mg/kg) was injected subcutaneously in female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO). As controls, we used rats treated with ethanol and saline vehicle (VEH). Insertion of a polyethylene catheter through the bladder dome and MCAO were performed using halothane anesthesia. The effects of intravenous (0.2 to 2000 nM/kg) or intravesical (0.2 or 2 nM) tolterodine, an antimuscarinic agent, on cystometrography were investigated in conscious rats with a cerebral infarct (CI). Tolterodine was instilled intravesically for 30 minutes and cystometry was repeated. RESULTS: Bladder capacity (BC) was markedly decreased after MCAO in RTX treated (RTX-CI) and VEH treated (VEH-CI) rats. Low tolterodine doses (0.2 or 2 nM/kg) significantly increased BC in VEH-CI rats without increasing residual volume but it had no effects on BC in RTX-CI rats. At the highest dose (2,000 nM/kg) the drug significantly decreased bladder contraction pressure and increased residual volume in RTX-CI and VEH-CI rats. Intravesical administration of tolterodine (0.2 or 2 nM) significantly increased BC in VEH-CI rats. However, tolterodine had no effect on BC in RTX-CI rats. CONCLUSIONS: These results suggest that at low doses tolterodine exerts an inhibitory effect on C-fiber bladder afferent nerves, thereby, improving BC during the storage phase.

Administration, Intravesical↗
PubMed2005

Direct effect of CoC12 and NiCl2 on citrate uptake by the rat renal brush border membrane.

Co and Ni are essential but relatively rare elements as to organisms. In the mammalian membrane, these metals are transported by the same carrier proteins. The aim of this study was to investigate the direct effects of CoCl2 and NiCl2 on citrate uptake by rat renal brush border membrane vesicles (BBMV). BBMV were prepared by the divalent cation precipitation methods, and citrate uptake was measured by the Millipore rapid membrane filtration technique. The time course of citrate uptake during 120-min of incubation with 1 mM CoCl2 and NiCl2 showed a rapid significant inhibition at the early phase and a slight recover at the late phase. Incubation for 1 min of BBMV with 1, 5 and 25 mM CoCl2 and NiCl2, respectively, significantly inhibited citrate uptake in a concentration-dependent manner compared with that of 0 mM. We discuss these findings from the point of view that Co and Ni are located in Group VIII of the periodic table.

Animals↗
PubMed2005

["Pathophysiology and treatment of the overactive bladder"].

The International Continence Society (ICS) recently derived a consensus symptomatic definition of overactive bladder (OAB) as urinary urgency, with or without urge incontinence, usually with frequency and nocturia. These symptom combinations are suggestive of urodynamically demonstrable detrusor overactivity. The etiology of OAB falls into two broad categories: neurogenic and nonneurogenic. It is not easy to confirm the etiology of OAB in patients with bladder outlet obstruction and neurological disease. This debate has attempted to examine the pathophysiology of OAB and to determine the optimal treatment strategy in a patient with two diseases possibly causing OAB. A 75-year-old man visited our hospital due to symptoms of OAB (urgency, nocturia, and urge incontinence) occurring after cerebrovascular accidents. Urge incontinence worsened concomitantly with the appearance of turbid urine. Urinary tract infection was accompanied by 84 ml of post-void residual. The prostate volume and PSA value were 28 ml and 1.2 ng/ml, respectively. The total International Prostate Symptom Score (IPSS) and Quality of Life (QOL) Index were 23 and 5, respectively. IPSS for storage symptoms was higher than that for obstructive symptoms. The maximum flow rate, measured after treatment for UTI, was 9.4 ml/s. Two debaters discuss the treament modality, TURP, or pharmacotherapy.

Aged↗
PubMed2004

Localization of hRad9, hHus1, hRad1, and hRad17 and caffeine-sensitive DNA replication at the alternative lengthening of telomeres-associated promyelocytic leukemia body.

Telomere maintenance is essential for continued cell proliferation. Although most cells accomplish this by activating telomerase, a subset of immortalized tumors and cell lines do so in a telomerase-independent manner, a process called alternative lengthening of telomeres (ALT). DNA recombination has been shown to be involved in ALT, but the precise mechanisms remain unknown. A fraction of cells in a given ALT population contain a unique nuclear structure called APB (ALT-associated promyelocytic leukemia (PML) body), which is characterized by the presence of telomeric DNA in the PML body. Here we describe that hRad9, hHus1, and hRad1, which form a DNA clamp complex that is associated with DNA damage, as well as its clamp loader, hRad17, are constitutive components of APB. Phosphorylated histone H2AX (gamma-H2AX), a molecular marker of double-strand breaks (DSBs), also colocalizes with some APBs. The results suggest that telomeric DNAs at APBs are recognized as DSBs. PML staining and fluorescence in situ hybridization analyses of mitotic ALT cells revealed that telomeric DNAs present at APBs are of both extrachromosomal and native telomere origins. Furthermore, we demonstrated that DNA synthesis occurs at APBs and is significantly inhibited by caffeine, an inhibitor of phosphatidylinositol 3-kinase-related kinases. Taken together, we suggest that telomeric DNAs at APBs are recognized and processed as DSBs, leading to telomeric DNA synthesis and thereby contributing to telomere maintenance in ALT cells.

Bromodeoxyuridine↗
PubMed2004

A mechanism of induction of the mouse zinc-fingers and homeoboxes 1 (ZHX1) gene expression by interleukin-2.

The effect of IL-2 on the expression of the mouse zinc-fingers and homeoboxes 1 (ZHX1) gene was investigated in a mouse cytotoxic T cell line, CTLL-2 cells. IL-2 specifically induced the expression of ZHX1 mRNA. The level of ZHX1 mRNA was decreased in the absence of IL-2. These alterations were in parallel with the status of cell proliferation. The signaling pathways involved in the induction were examined. AG-490, wortmannin, and LY294002 blocked the induction by IL-2. Nuclear run-on assays and a mRNA stability analysis revealed that the half-life of ZHX1 mRNA but not the transcription rate of the gene was increased by IL-2. Thus, we conclude that IL-2 induces the expression of the mouse ZHX1 gene in CTLL-2 cells, that both Janus kinase 3/signal transducer and activator of transcription 5 and phosphoinositide 3-kinase pathways are involved in the induction, and that the increased mRNA stability results in the induction.

Animals↗