Loss of Caveolin 1 is Associated With the Expression of Aquaporin 1 and Bladder Dysfunction in Mice / 대한배뇨장애요실금학회지

PURPOSE: It is suggested that caveolin and aquaporin might be closely associated with bladder signal activity. We investigated the effect of the deletion of caveolin 1, using caveolin 1 knockout mice, on the expression of aquaporin 1 in order to identify their relation in the urothelium of the urinary bladder. METHODS: The cellular localization and expressions of aquaporin 1 and caveolin 1, in the wild type and caveolin 1 knockout mice urinary bladder, were examined by Western blot and immunofluorescence techniques. RESULTS: Aquaporin 1 and caveolin 1 were coexpressed in the arterioles, venules, and capillaries of the suburothelial layer in the wild type controls. Aquaporin 1 protein expression was significantly higher in the caveolin 1 knockout mice than in the wild type controls (P <0.05). CONCLUSIONS: The results imply that aquaporin 1 and caveolin 1 may share a distinct relation with the bladder signal activity. This might play a specific role in bladder dysfunction.

Overexpression of Aquaporin-1 and Caveolin-1 in the Rat Urinary Bladder Urothelium Following Bladder Outlet Obstruction / 대한배뇨장애요실금학회지

PURPOSE: This study was designed to investigate the effect of detrusor overactivity induced by partial bladder outlet obstruction (BOO) on the expression of aquaporin 1 (AQP1) and caveolin 1 (CAV1) in the rat urinary bladder, and to determine the role of these molecules in detrusor overactivity. METHODS: Female Sprague-Dawley rats were divided into control (n=30) and experimental (n=30) groups. The BOO group underwent partial BOO, and the control group underwent a sham operation. After 4 weeks, an urodynamic study was performed to measure the contraction interval and contraction pressure. The expression and cellular localization of AQP1 and CAV1 were determined by western blot and immunofluorescence experiments in the rat urinary bladder. RESULTS: In cystometrograms, the contraction interval was significantly lower in the BOO group (2.9+/-1.5 minutes) than in the control group (6.7+/-1.0 minutes) (P<0.05). Conversely, the average contraction pressure was significantly higher in the BOO group (21.2+/-3.3 mmHg) than in the control group (13.0+/-2.5 mmHg) (P<0.05). AQP1 and CAV1 were coexpressed in the capillaries, arterioles, and venules of the suburothelial layer. AQP1 and CAV1 protein expression was significantly increased in the BOO rats compared to the control rats (P<0.05). CONCLUSIONS: Detrusor overactivity induced by BOO causes a significant increase in the expression of AQP1 and CAV1, which were coexpressed in the suburothelial microvasculature. This finding suggests that AQP1 and CAV1 might be closely related to bladder signal activity and may have a functional role in BOO-associated detrusor overactivity.

Expression and Localization of Aquaporins in Benign Prostate Hyperplasia and Prostate Cancer / 전남의대학술지

The aquaporin (AQP) families of water channels are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. The purposes of this study were to determine the expression and localization of AQPs in benign prostatic hyperplasia and prostate cancer. Prostatic tissue was collected from patients with benign prostatic hyperplasia or prostate cancer by transurethral resection of the prostate. The expression and cellular localization of the AQPs were determined in the human prostate by Western blot and immunohistochemistry. AQP1, 3, and 9 were expressed in the human prostate. Western blot analysis revealed bands at 28-36 kDa for the AQP1, 3, and 9 proteins. Of these proteins, AQP3 and 9 were expressed in the epithelium. Immunolabeling showed that AQP1 was mainly expressed in the capillaries and venules of the prostate, AQP9 was expressed in the cytoplasm of the epithelium, and AQP3 was mainly associated with the plasma membrane of the prostatic epithelium. Only AQP3 expression was localized in the cell membrane, and expressed AQP3 was translocated to the cytoplasm in prostate cancer. The epithelium in the human prostate expresses AQP3 and 9 proteins, and the capillaries and venules of the prostate express AQP1. Characterizing or modifying the expression of AQP3 may lead to an understanding of the role of the AQPs in human prostatic disease.

Expression of Caveolin-1 in Rat Urinary Bladder with Cyclophosphamide-Induced Cystitis / 대한배뇨장애요실금학회지

PURPOSE: The purposes of this study were to investigate the effect of cyclophosphamide (CYP)-induced inflammatory cystitis on caveolin 1 in rat urinary bladder and to determine the role of these molecules in the bladder dysfunction that occurs in inflammatory change in rat urinary bladder. METHODS: Female Sprague-Dawley rats were divided into control (n=30) and experimental (n=30) groups. Cystitis in experimental group was induced by intraperitoneal injection of CYP (200 mg/kg). The control group underwent an intraperitoneal saline injection. After 3 days, urodynamic studies were done to measure the contraction interval and contraction pressure. The expression and cellular localization of caveolin 1 were determined by Western blot and immunofluorescent study in rat urinary bladder. RESULTS: In cystometrograms, the contraction interval (minute) was significantly increased in the CYP-induced cystitis rats (15.8+/-1.5) than in the control group (6.3+/-0.5) (P<0.05). Conversely, the average contraction pressure (mmHg) was significantly higher in the CYP-induced cystitis rats (15.6+/-1.7) than in the control group (11.3+/-0.5) (P<0.05). Caveolin 1 was expressed in the capillaries, arteriols and venules. The protein expression of caveolin 1 was significantly decreased in the CYP-induced cystitis rats (P<0.05). CONCLUSIONS: Inflammatory change of urinary bladder maybe causes a significant change in the expression of caveolin 1. These findings suggest that caveolin 1 might have a functional role in the bladder dysfunction related with cystitis in rat urinary bladder.

Expression and Localization of Aquaporins in Benign Prostate Hyperplasia and Prostate Cancer / 전남의대학술지

The aquaporin (AQP) families of water channels are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. The purposes of this study were to determine the expression and localization of AQPs in benign prostatic hyperplasia and prostate cancer. Prostatic tissue was collected from patients with benign prostatic hyperplasia or prostate cancer by transurethral resection of the prostate. The expression and cellular localization of the AQPs were determined in the human prostate by Western blot and immunohistochemistry. AQP1, 3, and 9 were expressed in the human prostate. Western blot analysis revealed bands at 28-36 kDa for the AQP1, 3, and 9 proteins. Of these proteins, AQP3 and 9 were expressed in the epithelium. Immunolabeling showed that AQP1 was mainly expressed in the capillaries and venules of the prostate, AQP9 was expressed in the cytoplasm of the epithelium, and AQP3 was mainly associated with the plasma membrane of the prostatic epithelium. Only AQP3 expression was localized in the cell membrane, and expressed AQP3 was translocated to the cytoplasm in prostate cancer. The epithelium in the human prostate expresses AQP3 and 9 proteins, and the capillaries and venules of the prostate express AQP1. Characterizing or modifying the expression of AQP3 may lead to an understanding of the role of the AQPs in human prostatic disease.

Effects of Estrogens on the Expression of Caveolin-1 in the Urinary Bladders of Female Rats / 대한배뇨장애요실금학회지

PURPOSE: The purposes of this study were to investigate the effect of hormonal alterations on the expression of caveolin-1 in the urinary bladders of ovariectomized rats and to determine the role of caveolin-1 in the overactivity of the detrusor muscle that occurs with hormonal alterations in rats. METHODS: Female Sprague-Dawley rats were divided into three groups: a control group, a group that underwent bilateral ovariectomy (Ovx), and a group that underwent bilateral ovariectomy followed by subcutaneous injections of 17beta-estradiol (Ovx+Est). After 4 weeks, urodynamic studies were done to measure the contraction interval and contraction pressure. The expression and cellular localization of caveolin-1 were determined by Western blot and immunofluorescence in the urinary bladders of rats. RESULTS: On cystometrograms, the contraction interval was significantly shorter in the Ovx group (3.0+/-0.3 minute) than in the control group (5.6+/-0.5 minute) but was longer in the Ovx+Est group (9.2+/- 0.4 minute) (P<0.05). Conversely, the average contraction pressure was higher in the Ovx group (26.4+/-0.48 mmHg) than in the control group (21.8+/-0.37 mmHg) but was lower in the Ovx+Est group (23.9+/-0.76 mmHg) (P<0.05). Caveolin-1 was expressed in the capillaries, arterioles, and venules. Expression of the protein caveolin-1 was significantly lower after ovariectomy and was restored to control levels after treatment with 17beta-estradiol (P<0.05). CONCLUSIONS: Hormonal alterations cause a significant change in the expression of caveolin-1, which suggests that caveolin-1 might have a functional role in the overactivity of the detrusor muscle related to hormonal alterations in the urinary bladders of rats.

Distribution of Interstitial Cells of Cajal in Menopausal Rat Urinary Bladder Showing Detrusor Overactivity / 대한배뇨장애요실금학회지

PURPOSE: Recent studies have showed that interstitial cells of Cajal (ICCs) are widely distributed in the genitourinary tract and have suggested their involvement in spontaneous electrical activity and muscle contraction. The purposes of this study were to investigate the effect of estrogen on ICCs in rat urinary bladder from the detrusor overactivity induced by ovariectomy. MATERIALS AND METHODS: Female Sprague-Dawley rats (230-240 g, N=60) were divided into three groups: control (N=20), bilateral ovariectomy (Ovx, N=20), and bilateral ovariectomy followed by subcutaneous injections of 17 beta-estradiol (50 mg/kg/day, Ovx + Est, N=20). After 4 weeks, urodynamic studies measuring contraction interval and contraction pressure were done. The cellular localization of ICCs was determined by immunohistochemistry in the rat urinary bladder. RESULTS: Filling cystometry studies demonstrated a reduced interval between voiding contractions and an increased voiding pressure in Ovx group. The approximate the contraction interval (min) was (3.9+/-0.25) significantly decreased in the Ovx group compared to the control group (6.7+/-0.15), which was increased after estrogen treatment (9.7+/-0.22) (p<0.05). Conversely, the average contraction pressures (mmHg) were increased in the Ovx group (28.9+/-2.1) compared to the control group (21.2+/-1.45), and decreased after estrogen treatment (24.8+/-2.21) (p<0.05). The population of c-Kit immunoreactive ICCs was decreased in both the urothelial and muscle layers in Ovx bladders, which increased to the control value after estrogen treatment. CONCLUSIONS: These results demonstrated an decreased immunoreactivity of ICCs in the menopausal rat model and suggest that thedecreased population of ICCs expression may contribute to the modulation of bladder overactivity induced by menopause.

The Expression of AQP1 and eNOS in Menopausal Rat Urinary Bladder / 대한배뇨장애요실금학회지

PURPOSE: Aquaporins (AQPs) have been reported to be expressed in rat and human urothelium. Nitric oxide (NO) is thought to play an important role in the bladder overactivity related to menopause. The purpose of this study was to investigate the effect of hormonal alteration on the expression of AQP1 and eNOS in menopausal rat urinary bladder. MATERIALS AND METHODS: Female Sprague-Dawley rats (230-240 g, N=30) were divided into three groups: control (N=10), bilateral ovariectomy (Ovx, N=10), and bilateral ovariectomy followed by subcutaneous injections of 17beta-estradiol (50 mg/kg/day, Ovx+Est, N=10). After 4 weeks, urodynamic studies measuring the contraction interval and contraction pressure were done. The expression and cellular localization of AQP1 and eNOS were determined by performing Western blotting and immunohistochemistry on the rat urinary bladder. RESULTS: The approximate contraction interval (min) was significantly decreased in the Ovx group (3.9+/-0.25) compared to the control group (6.7+/-0.15), and was increased after estrogen treatment (9.7+/-0.22) (p<0.05). The AQP1 and eNOS immunoreactivities were localized in the same areas: capillaries, arterioles, and venules of the lamina propria. The protein expression of AQP1 was not changed significantly, whereas eNOS expression was significantly decreased in the Ovx group and restored to the control value in the Ovx+Est group. CONCLUSIONS: This study showed that ovariectomy causes a significant change in e-NOS expression without a change in AQP1 in menopausal rat urinary bladder. This may imply that e-NOS has a functional role in the bladder overactivity that occurs in association with menopause.

Changes in Aquaporin 1 Expression in Rat Urinary Bladder after Partial Bladder Outlet Obstruction: Preliminary Report

PURPOSE: Aquaporins (AQPs) are membrane proteins that facilitate water movement across biological membranes. AQPs are also called water channels, and they have recently been reported to be expressed in rat and human urothelium. The purposes of this study were to investigate the effect of bladder outlet obstruction (BOO) on the rat urothelium and AQP1 expression in rat urothelium. MATERIALS AND METHODS: Female Sprague-Dawley rats (230-240 g each, n=20) were divided into 2 groups: the sham group (the Con group, n=10) and the partial BOO group (the BOO group, n=10). The BOO group underwent a partial BOO. The expression and cellular localization of AQP1 were determined by performing Western blotting and immunohistochemistry on the rat urinary bladder. RESULTS: AQP1 immunoreactivity in both the control and the BOO groups was localized in the capillaries, arterioles, and venules of the lamina propria of the urinary bladder. The protein expression of AQP1 was significantly increased in the BOO group. CONCLUSIONS: This study showed that BOO causes a significant increase in the expression of AQP1. This may imply that AQP1 has a functional role in the detrusor instability that occurs in association with BOO.

Study on mechanism of multistep hepatotumorigenesis in rat: development of hepatotumorigenesis

With the aim of establishing bio-indices for the development of multistep hepatotumorigenesis, rats were fed water containing 0.01% diethylnitrosamine (DEN) ad libitum for 13 weeks. This treatment with DEN only made it possible to induce hepatic tumors in 100%. After the DEN administration, several clinical symptoms were observed including minor behavioral changes, brittleness of hair and a decrease in water and food intake. The concentration of total serum protein and albumin in all treated groups was significantly lower than in non-treated controls (p<0.05). Increase of specific enzyme (AST, ALT and GGT) activity (p<0.05), variable tumor size and hepatomegaly of the liver was observed in all rats treated with DEN for 10 weeks. Both hepatocellular carcinoma and cholangiocarcinoma were found in the same livers at the same time, and were prominently developed after 12 weeks. In case of carcinoma, some of the livers showed more or less advanced states over the 12-15 weeks period. In the present study, hepatocellular carcinoma was developed by treating DEN in only the drinking water, without any other carcinogens or without partial hepatectomy. These results indicate that DEN is a new carcinogen that acts directly on it the liver, moreover, it might be very useful for investigating hepatotumorigenesis.