Plasticity of cytochrome P450 isozyme expression in rat trigeminal ganglia neurons during inflammation.
Plasticity of cytochrome P450 isozyme expression in rat trigeminal ganglia neurons during inflammation.
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DOI：
10.1016/j.pain.2012.04.027
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发表时间：
2012-10
期刊：
影响因子：
7.4
通讯作者：
Hargreaves KM
中科院分区：
文献类型：
--
作者：
Ruparel S;Henry MA;Akopian A;Patil M;Zeldin DC;Roman L;Hargreaves KM
最近，特异性氧化亚油酸代谢物（OLAMs）已被确定为瞬时受体电位香草样蛋白1 （TRPV1）通道激动剂，有助于炎症和热痛觉机制，但感觉神经元中OLAM合成的具体机制尚不清楚。在这里，我们使用分子、解剖、钙成像和穿孔补丁电生理学方法来证明细胞色素P450酶（CYPs）在亚油酸氧化导致神经元活化中的特异性参与，并表明这种作用在炎症条件下得到增强。其他研究评估了CYP在天然大鼠三叉神经节（TG）组织和培养物中的表达，以及诱导外周炎症后其表达模式的变化。在天然TG中检测到20个候选转录本中的14个，其中7个在培养条件下表现出表达改变。此外，完全弗氏佐剂诱导的振动垫炎症选择性地增加了TG中CYP3A23/3A1和CYP2J4转录本的表达。原位杂交研究表明，CYP3A23/3A1和CYP2J4在TG神经元中广泛表达。解剖研究表明，包括TRPV1在内的TG感觉神经元中存在CYP3A1和CYP2J家族的表达，约一半TRPV1阳性神经元CYP3A1和CYP2J的表达更为突出。总之，这些发现表明，CYP酶在介导亚油酸诱发的感觉神经元激活中起主要作用，并进一步暗示特定CYP参与了olam的形成，olam在这一伤害感受器亚群中充当TRPV1激动剂。
Recently, specific oxidized linoleic acid metabolites (OLAMs) have been identified as transient receptor potential vanilloid 1 (TRPV1) channel agonists that contribute to inflammatory and heat hyperalgesia mechanisms, yet the specific mechanism responsible for OLAM synthesis in sensory neurons is unknown. Here, we use molecular, anatomical, calcium imaging and perforated patch electrophysiology methods to demonstrate the specific involvement of cytochrome P450 enzymes (CYPs) in the oxidation of linoleic acid leading to neuronal activation and show that this is enhanced under inflammatory conditions. Additional studies evaluated CYP expressions in the native rat trigeminal ganglia (TG) tissue and cultures as well as changes in their expression pattern following the induction of peripheral inflammation. Fourteen of twenty candidate transcripts were detected in native TG and seven of these displayed altered expression under cultured conditions. Moreover, complete Freund’s adjuvant-induced inflammation of vibrissal pad selectively increased expression of CYP3A23/3A1 and CYP2J4 transcripts in TG. In situ hybridization studies demonstrated broad expression pattern of CYP3A23/3A1 and CYP2J4 within TG neurons. Anatomical studies characterized the expression of CYP3A1 and the CYP2J families within TG sensory neurons including those with TRPV1, with about half of all TRPV1 positive neurons showing more prominent CYP3A1 and CYP2J expression. Together, these findings show that CYP enzymes play a primary role in mediating linoleic acid-evoked activation of sensory neurons and furthermore implicate the involvement of specific CYPs as contributing to the formation OLAMs that act as TRPV1 agonists within this subpopulation of nociceptors.
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影响因子：
4.7
作者：
Iliff JJ;Fairbanks SL;Balkowiec A;Alkayed NJ
通讯作者：
Alkayed NJ
影响因子：
5
作者：
Deng Y;Theken KN;Lee CR
通讯作者：
Lee CR
DOI：
10.1016/s0169-328x(03)00335-8
发表时间：
2003-10-21
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Dussor, GO;Price, TJ;Flores, CM
通讯作者：
Flores, CM
影响因子：
8.8
作者：
Hall, Naeemah K.;Chapman, Timothy M.;Min, David B.
通讯作者：
Min, David B.
影响因子：
5.3
作者：
Diogenes, Anibal;Patwardhan, Amol M.;Hargreaves, Kenneth M.
通讯作者：
Hargreaves, Kenneth M.