Phosphorylation of extracellular signal-regulated kinases in bladder afferent pathways with cyclophosphamide-induced cystitis.
Phosphorylation of extracellular signal-regulated kinases in bladder afferent pathways with cyclophosphamide-induced cystitis.
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DOI：
10.1016/j.neuroscience.2009.07.044
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发表时间：
2009-11-10
期刊：
影响因子：
3.3
通讯作者：
Vizzard, M. A.
中科院分区：
文献类型：
--
作者：
Corrow, K. A.;Vizzard, M. A.
细胞外信号调节激酶（ERK 1和ERK 2）在躯体或内脏刺激或炎症后在神经系统中磷酸化，并在中枢敏化和疼痛超敏性中发挥作用。ERK 1/2激活与CYP诱导的膀胱炎已在膀胱中得到证实，ERK 1/2磷酸化抑制剂可减少CYP诱导的膀胱反射亢进。在这项研究中，我们确定pERK 1/2的表达和调节在腰骶背根神经节（DRG）和脊髓与环磷酰胺（CTX）诱导的膀胱炎（4小时（小时），48小时，慢性）使用蛋白质印迹和免疫组织化学技术。CYP诱导的膀胱炎在L6和S1 DRG中pERK 1/2表达显著上调（p ≤ 0.01），最大上调发生在4小时。CYP诱导的膀胱炎在L1、L2或L5 DRG或任何脊髓节段（L1、L2、L5-S1）中未观察到pERK 1/2表达的变化。在对照组大鼠的所有DRG中均观察到细胞质pERK 1/2-免疫反应性（IR）和细胞周pERK 1/2-IR，在CYP诱导的膀胱炎4小时和48小时的L6和S1 DRG中，细胞质pERK 1/2-IR显著增加（p ≤ 0.01）。相反，DRG中细胞周围的pERK 1/2-IR不受CYP诱导的膀胱炎的调节。对照组大鼠腰骶背根节内少量膀胱传入细胞表达pERK 1/2-IR;但是，在此情况下，CYP诱导的膀胱炎（48 h）显著（p ≤ 0.01）增加了L6和S1 DRG中表现出pERK 1/2-IR的膀胱传入细胞的百分比。这些研究表明，腰骶DRG中ERK通路的激活可能在排尿反射的神经可塑性中起作用。诱发膀胱炎。
Extracellular signal-regulated kinases (ERK1 and ERK2) are phosphorylated in the nervous system after somatic or visceral stimulation or inflammation and play roles in central sensitization and pain hypersensitivity. ERK1/2 activation with CYP-induced cystitis has been demonstrated in urinary bladder and inhibitors of ERK1/2 phosphorylation reduce CYP-induced bladder hyperreflexia. In this study, we determined pERK1/2 expression and regulation in lumbosacral dorsal root ganglia (DRG) and spinal cord with cyclophosphamide (CYP)-induced cystitis (4 hour (hr), 48 hr, chronic) using western blotting and immunohistochemical techniques. pERK1/2 expression was significantly (p ≤ 0.01) upregulated in L6 and S1 DRG with CYP-induced cystitis with the greatest upregulation occurring at 4 hr. No changes in pERK1/2 expression were observed in L1, L2 or L5 DRG or in any spinal cord segment examined (L1, L2, L5-S1) with CYP-induced cystitis. Cytoplasmic pERK1/2-immunoreactivity (IR) and pericellular pERK1/2-IR was observed in all DRG examined from control rats and cytoplasmic pERK1/2-IR was significantly (p ≤ 0.01) increased in L6 and S1 DRG with 4 hr and 48 hr CYP-induced cystitis. In contrast, pericellular pERK1/2-IR in DRG was not regulated by CYP-induced cystitis. A small percentage of bladder afferent cells in lumbosacral DRG expressed pERK1/2-IR in control rats; however, CYP-induced cystitis (48 hr) significantly (p ≤ 0.01) increased the percentage of bladder afferent cells in the L6 and S1 DRG exhibiting pERK1/2-IR. These studies suggest that activation of the ERK pathway in lumbosacral DRG may play a role in neuroplasticity in micturition reflexes with CYP-induced cystitis.
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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：
4.6
作者：
Malley, SE;Vizzard, MA
通讯作者：
Vizzard, MA
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：
6.6
作者：
Driscoll, A;Teichman, JMH
通讯作者：
Teichman, JMH
影响因子：
2.5
作者：
KEAST, JR;DEGROAT, WC
通讯作者：
DEGROAT, WC