Uric acid suppresses 1 alpha hydroxylase in vitro and in vivo.
Uric acid suppresses 1 alpha hydroxylase in vitro and in vivo.
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DOI：
10.1016/j.metabol.2013.09.018
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发表时间：
2014-01
影响因子：
9.8
通讯作者：
Jalal, Diana
中科院分区：
文献类型：
--
作者：
Chen, Wei;Roncal-Jimenez, Carlos;Lanaspa, Miguel;Smits, Gerard;Chonchol, Michel;Johnson, Richard J.;Jalal, Diana
痛风患者骨化三醇水平较低，当尿酸降低时，骨化三醇水平会改善。这些观察的机制尚不清楚。我们假设尿酸抑制1- α羟化酶。在体内，Sprague Dawley大鼠随机分为对照组（n=5）、allantoxanamide组（n=8）、非布司他组（n=5）或allantoxanamide+非布司他组（n=7）。测定维生素D、甲状旁腺素和1-α羟化酶蛋白。为了直接评价尿酸对1-α羟化酶的影响，我们在体外进行了一系列剂量反应和时间过程实验。核因子κ-B （NFκB）在药理学上受到抑制。最后，为了评估这些发现对人类的潜在影响，在对NHANES（2003-2006）数据的横断面分析中评估了人类尿酸和甲状旁腺激素之间的关系；n = 9773。1,25(OH)2D和1-α羟化酶蛋白在高尿酸血症大鼠中降低，非布司他治疗后改善。尿酸抑制近端小管细胞1-α羟化酶蛋白及mRNA表达。这可通过抑制NFκB来阻止。在人类中，对于所有受试者、估计GFR≥60的受试者和估计GFR <60 mL/min/1.73 m2的受试者，尿酸每增加1 mg/dL， PTH升高（bbb65 pg/mL）的校正优势比分别为1.21 （95% C.I. 1.14, 1.28， P<0.0001）、1.15 （95% C.I. 1.08, 1.22， P<0.0001）和1.16 （95% C.I. 1.03, 1.31， P=0.02）。高尿酸血症抑制1-α羟化酶，导致大鼠125 (OH)2D降低，甲状旁腺激素升高。我们的结果表明这是由NFκB介导的。在NHANES中，尿酸和甲状旁腺激素之间的关联提示了对人类疾病的潜在影响。
Patients with gout have lower calcitriol levels that improve when uric acid is lowered. The mechanism of these observations is unknown. We hypothesized that uric acid inhibits 1- αhydroxylase. In vivo, Sprague Dawley rats were randomized to control (n=5), allantoxanamide (n=8), febuxostat (n=5), or allantoxanamide+febuxostat (n=7). Vitamin D, PTH, and 1-αhydroxylase protein were evaluated. In order to directly evaluate the effect of uric acid on 1-αhydroxylase, we conducted a series of dose response and time course experiments in vitro. Nuclear factor κ-B (NFκB) was inhibited pharmacologically. Finally, to evaluate the potential implications of these findings in humans, the association between uric acid and PTH in humans was evaluated in a cross-sectional analysis of data from the NHANES (2003-2006); n= 9773. 1,25(OH)2D and 1-αhydroxylase protein were reduced in hyperuricemic rats and improved with febuxostat treatment. Uric acid suppressed 1-αhydroxylase protein and mRNA expression in proximal tubular cells. This was prevented by NFκB inhibition. In humans, for every 1 mg/dL increase in uric acid, the adjusted odds ratio for an elevated PTH (>65 pg/mL) was 1.21 (95% C.I. 1.14, 1.28; P< 0.0001), 1.15 (95% C.I. 1.08, 1.22; P<0.0001), and 1.16 (95% C.I. 1.03, 1.31; P=0.02) for all subjects, subjects with estimated GFR ≥60, and subjects with estimated GFR <60 mL/min/1.73 m2 respectively. Hyperuricemia suppresses 1-αhydroxylase leading to lower 1,25(OH)2D and higher PTH in rats. Our results suggest this is mediated by NFκB. The association between uric acid and PTH in NHANES suggests potential implications for human disease.
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DOI：
10.1152/ajprenal.00104.2006
发表时间：
2007-01-01
影响因子：
4.2
作者：
Han, Ho Jae;Lim, Min Jin;Taub, Mary
通讯作者：
Taub, Mary
影响因子：
4.8
作者：
McCullough, Peter A.;Li, Suying;Bakris, George L.
通讯作者：
Bakris, George L.
影响因子：
--
作者：
Ebert, R;Jovanovic, M;Jakob, F
通讯作者：
Jakob, F
DOI：
10.1111/j.1464-410x.1987.tb04863.x
发表时间：
1987-06-01
期刊：
BRITISH JOURNAL OF UROLOGY
影响因子：
--
作者：
KOHRI, K;TAKADA, M;KURITA, T
通讯作者：
KURITA, T
影响因子：
3.3
作者：
Saleh, F;Jorde, R;Figenschau, Y
通讯作者：
Figenschau, Y