NLRP3 activation contributes to endothelin-1-induced erectile dysfunction.
NLRP3 activation contributes to endothelin-1-induced erectile dysfunction.
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DOI：
10.1111/jcmm.17463
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发表时间：
2023-01
影响因子：
5.3
通讯作者：
Silva Carneiro, Fernando
中科院分区：
文献类型：
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作者：
Sobrano Fais, Rafael;Menezes da Costa, Rafael;Carvalho Mendes, Allan;Mestriner, Fabiola;Comerma-Steffensen, Simon Gabriel;Tostes, Rita C.;Simonsen, Ulf;Silva Carneiro, Fernando
在本研究中，我们假设内皮素（ET）受体（ETA和ETB）刺激，通过增加钙和ROS的形成，导致核苷酸寡聚化结构域样受体家族，Pyrin结构域3 （NLRP3）激活。测量C57BL/6 （WT）小鼠海绵体内压（ICP/MAP）。在ET‐1 （100 nM）和载体、MCC950、铁、BAPTA AM、BQ123或BQ788存在的情况下，对WT、NLRP3−/−和caspase−/−小鼠海底体（CC）条进行功能和免疫印迹分析。ET‐1降低了WT小鼠的ICP/MAP， MCC950阻止了ET‐1的作用。ET‐1降低CC ACh‐，硝普钠（SNP）诱导的松弛，增加caspase‐1的表达。ETA受体拮抗剂BQ123逆转了这一效应。ETB受体拮抗剂BQ788也逆转了ET‐1对ACh和SNP松弛的抑制。此外，铁、BAPTA AM和NLRP3基因缺失阻止了ET - 1诱导的ACh丢失和SNP松弛。此外，BQ123降低了CC caspase‐1的表达，而BQ788以浓度依赖性的方式（100 nM-10 μM）增加了caspase‐1和IL‐1β的表达。此外，铁和BAPTA AM可阻止ET - 1诱导的caspase - 1升高。此外，BAPTA AM阻断ET‐1‐诱导的ROS生成。总之，ET‐1诱导的勃起功能障碍依赖于ETA‐和ETB‐通过Ca2+依赖性ROS生成介导的小鼠CC中NLRP3的激活。
In the present study, we hypothesized that endothelin (ET) receptors (ETA and ETB) stimulation, through increased calcium and ROS formation, leads to Nucleotide Oligomerization Domain‐Like Receptor Family, Pyrin Domain Containing 3 (NLRP3) activation. Intracavernosal pressure (ICP/MAP) was measured in C57BL/6 (WT) mice. Functional and immunoblotting assays were performed in corpora cavernosa (CC) strips from WT, NLRP3−/− and caspase−/− mice in the presence of ET‐1 (100 nM) and vehicle, MCC950, tiron, BAPTA AM, BQ123, or BQ788. ET‐1 reduced the ICP/MAP in WT mice, and MCC950 prevented the ET‐1 effect. ET‐1 decreased CC ACh‐, sodium nitroprusside (SNP)‐induced relaxation, and increased caspase‐1 expression. BQ123 an ETA receptor antagonist reversed the effect. The ETB receptor antagonist BQ788 also reversed ET‐1 inhibition of ACh and SNP relaxation. Additionally, tiron, BAPTA AM, and NLRP3 genetic deletion prevented the ET‐1‐induced loss of ACh and SNP relaxation. Moreover, BQ123 diminished CC caspase‐1 expression, while BQ788 increased caspase‐1 and IL‐1β levels in a concentration‐dependent manner (100 nM–10 μM). Furthermore, tiron and BAPTA AM prevented ET‐1‐induced increase in caspase‐1. In addition, BAPTA AM blocked ET‐1‐induced ROS generation. In conclusion, ET‐1‐induced erectile dysfunction depends on ETA‐ and ETB‐mediated activation of NLRP3 in mouse CC via Ca2+‐dependent ROS generation.
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影响因子：
6.1
作者：
De Giusti, V. C.;Correa, M. V.;Aiello, E. A.
通讯作者：
Aiello, E. A.
影响因子：
9.5
作者：
Browatzki, M;Schmidt, J;Kranzhöfer, R
通讯作者：
Kranzhöfer, R
胰岛素耐受性肥胖扎克大鼠阴茎动脉中与内皮素 B 型受体耦合的内皮素钙信号受损
影响因子：
3.5
作者：
Contreras, Cristina;Sanchez, Ana;Prieto, Dolores
通讯作者：
Prieto, Dolores
影响因子：
4.6
作者：
HELSET, E;SILDNES, T;KONOPSKI, ZS
通讯作者：
KONOPSKI, ZS
影响因子：
30.5
作者：
通讯作者：
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