Effects of estrogens and bladder inflammation on mitogen-activated protein kinases in lumbosacral dorsal root ganglia from adult female rats.
Effects of estrogens and bladder inflammation on mitogen-activated protein kinases in lumbosacral dorsal root ganglia from adult female rats.
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DOI：
10.1186/1471-2202-10-156
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发表时间：
2009-12-28
期刊：
影响因子：
2.4
通讯作者：
Keast JR
中科院分区：
文献类型：
--
作者：
Cheng Y;Keast JR
间质性膀胱炎是一种与膀胱炎症相关的慢性疾病，与许多其他慢性疼痛状态一样，与间质性膀胱炎相关的症状在女性中更常见，并在月经周期中波动。本研究的目的是确定雌激素是否可以直接调节膀胱感觉神经元内的信号通路，如细胞外信号相关激酶（ERK）和p38丝裂原活化蛋白（MAP）激酶。这些信号通路与炎症性躯体疼痛的神经元可塑性有关，但在内脏伤害感受器中尚未得到广泛研究。我们专注于腰骶背根神经节（DRG）神经元投射到盆腔脏器（L1，L2，L 6，S1）的成年雌性Sprague-Dawley大鼠，并进行了在体外和体内的操作，以比较短期和长期的雌激素水平的变化对MAPK的表达和激活的影响。我们还研究了长时间的雌激素剥夺是否会影响下尿路炎症对MAPK信号传导的影响。在短期（过夜）培养的分离DRG神经元的研究中，我们发现雌二醇和雌激素受体（ER）激动剂迅速刺激ER依赖性p38磷酸化相对于总p38。在体内慢性雌激素剥夺（卵巢切除术）后对DRG的检查显示总p38和磷酸化p38（相对于β-微管蛋白）平行增加。我们还观察到ERK 1磷酸化增加（相对于总ERK 1），但ERK 1表达无变化（相对于β-微管蛋白）。我们没有观察到ERK 2表达或磷酸化的变化。虽然卵巢切除术增加了磷酸化ERK 1的水平（与总ERK 1相比），但环磷酰胺诱导的下尿路炎症并没有导致ERK 1或ERK 2或其磷酸化的净增加。然而，炎症确实导致相对于β-微管蛋白的p38蛋白水平的增加。先前的卵巢切除术并没有改变炎症反应。这些结果为雌激素对膀胱伤害感受器信号传导的复杂影响提供了新的见解。这些神经节中雌激素作用的多样性提高了开发新方法来调节其在骨盆活动过度或疼痛状态下的功能的可能性。
Interstitial cystitis is a chronic condition associated with bladder inflammation and, like a number of other chronic pain states, symptoms associated with interstitial cystitis are more common in females and fluctuate during the menstrual cycle. The aim of this study was to determine if estrogens could directly modulate signalling pathways within bladder sensory neurons, such as extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases. These signalling pathways have been implicated in neuronal plasticity underlying development of inflammatory somatic pain but have not been as extensively investigated in visceral nociceptors. We have focused on lumbosacral dorsal root ganglion (DRG) neurons projecting to pelvic viscera (L1, L2, L6, S1) of adult female Sprague-Dawley rats and performed both in vitro and in vivo manipulations to compare the effects of short- and long-term changes in estrogen levels on MAPK expression and activation. We have also investigated if prolonged estrogen deprivation influences the effects of lower urinary tract inflammation on MAPK signalling. In studies of isolated DRG neurons in short-term (overnight) culture, we found that estradiol and estrogen receptor (ER) agonists rapidly stimulated ER-dependent p38 phosphorylation relative to total p38. Examination of DRGs following chronic estrogen deprivation in vivo (ovariectomy) showed a parallel increase in total and phosphorylated p38 (relative to β-tubulin). We also observed an increase in ERK1 phosphorylation (relative to total ERK1), but no change in ERK1 expression (relative to β-tubulin). We observed no change in ERK2 expression or phosphorylation. Although ovariectomy increased the level of phosphorylated ERK1 (vs. total ERK1), cyclophosphamide-induced lower urinary tract inflammation did not cause a net increase of either ERK1 or ERK2, or their phosphorylation. Inflammation did, however, cause an increase in p38 protein levels, relative to β-tubulin. Prior ovariectomy did not alter the response to inflammation. These results provide new insights into the complex effects of estrogens on bladder nociceptor signalling. The diversity of estrogen actions in these ganglia raises the possibility of developing new ways to modulate their function in pelvic hyperactivity or pain states.
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影响因子：
25
作者：
Ji, RR;Baba, H;Woolf, CJ
通讯作者：
Woolf, CJ
影响因子：
2.7
作者：
Bennett, HL;Gustafsson, JÅ;Keast, JR
通讯作者：
Keast, JR
影响因子：
5.8
作者：
COX, PJ
通讯作者：
COX, PJ
DOI：
10.1016/s0169-328x(03)00284-5
发表时间：
2003-08-19
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Galan, A;Cervero, F;Laird, JMA
通讯作者：
Laird, JMA
影响因子：
2.1
作者：
Bjorling, DE;Wang, ZY
通讯作者：
Wang, ZY