Isoprenoids increase bovine endometrial stromal cell tolerance to the cholesterol-dependent cytolysin from Trueperella pyogenes.
Isoprenoids increase bovine endometrial stromal cell tolerance to the cholesterol-dependent cytolysin from Trueperella pyogenes.
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DOI：
10.1093/biolre/ioy099
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发表时间：
2018-10-01
影响因子：
3.6
通讯作者：
Sheldon IM
中科院分区：
文献类型：
--
作者：
Griffin S;Healey GD;Sheldon IM
预防产后子宫疾病有赖于子宫内膜细胞对产后侵入子宫的细菌的耐受能力。黄牛产后子宫疾病和子宫内膜病变与化脓性螺旋体的病原菌关系最为密切。化脓性真皮杆菌分泌一种胆固醇依赖的细胞溶血素，溶血素通过在子宫内膜间质细胞质膜上形成孔洞而引起细胞溶解。本研究的目的是确定增加牛子宫内膜基质细胞对溶血素耐受性的细胞内在途径。溶血素可引起牛子宫内膜间质细胞的剂量依赖性细胞溶解和乳酸脱氢酶漏入上清液。针对甲氧戊酸和胆固醇合成途径的抑制剂可以增加细胞对溶血素的耐受性，但不能针对丝裂原激活的蛋白激酶、细胞周期或代谢途径。通过供应甲戊酸衍生的异戊二烯类法尼基焦磷酸，或通过抑制法尼基-二磷酸法尼基转移酶1或香叶基香叶基二磷酸合成酶1来增加法尼基焦磷的丰度，降低了细胞胆固醇，提高了细胞对溶血素的耐受性。供应甲羟戊酸衍生的异戊二烯类香叶基香叶基焦磷酸也增加了细胞对溶血素的耐受性，但与细胞胆固醇的变化无关。然而，香叶基香叶基焦磷酸抑制核受体亚家族1组H受体(NR1H，也称为肝X受体)，减少编码NR1H3或NR1H2的基因的表达，增加基质细胞对溶血素的耐受性。总而言之，甲氧戊酸衍生的异戊二烯类化合物增加了牛子宫内膜基质细胞对溶血素的耐受性，这与降低细胞胆固醇和抑制NR1H受体有关。甲羟戊酸衍生的异戊二烯类化合物，法尼基和香叶基焦磷酸，增加了牛子宫内膜基质细胞对子宫病原体化脓性真皮杆菌分泌的胆固醇依赖的细胞溶血素，溶血素的耐受性。
Preventing postpartum uterine disease depends on the ability of endometrial cells to tolerate the presence of the bacteria that invade the uterus after parturition. Postpartum uterine disease and endometrial pathology in cattle are most associated with the pathogen Trueperella pyogenes. Trueperella pyogenes secretes a cholesterol-dependent cytolysin, pyolysin, which causes cytolysis by forming pores in the plasma membrane of endometrial stromal cells. The aim of the present study was to identify cell-intrinsic pathways that increase bovine endometrial stromal cell tolerance to pyolysin. Pyolysin caused dose-dependent cytolysis of bovine endometrial stromal cells and leakage of lactate dehydrogenase into supernatants. Cell tolerance to pyolysin was increased by inhibitors that target the mevalonate and cholesterol synthesis pathway, but not the mitogen-activated protein kinase, cell cycle, or metabolic pathways. Cellular cholesterol was reduced and cell tolerance to pyolysin was increased by supplying the mevalonate-derived isoprenoid farnesyl pyrophosphate, or by inhibiting farnesyl-diphosphate farnesyltransferase 1 or geranylgeranyl diphosphate synthase 1 to increase the abundance of farnesyl pyrophosphate. Supplying the mevalonate-derived isoprenoid geranylgeranyl pyrophosphate also increased cell tolerance to pyolysin, but independent of changes in cellular cholesterol. However, geranylgeranyl pyrophosphate inhibits nuclear receptor subfamily 1 group H receptors (NR1H, also known as liver X receptors), and reducing the expression of the genes encoding NR1H3 or NR1H2 increased stromal cell tolerance to pyolysin. In conclusion, mevalonate-derived isoprenoids increased bovine endometrial stromal cell tolerance to pyolysin, which was associated with reducing cellular cholesterol and inhibiting NR1H receptors. Mevalonate-derived isoprenoids, farnesyl and geranylgeranyl pyrophosphate, increase bovine endometrial stromal cell tolerance to the cholesterol-dependent cytolysin, pyolysin, which is secreted by the uterine pathogen Trueperella pyogenes.
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影响因子：
64.5
作者：
Ayres JS
通讯作者：
Ayres JS
影响因子：
3.6
作者：
Cronin JG;Turner ML;Goetze L;Bryant CE;Sheldon IM
通讯作者：
Sheldon IM
影响因子：
3.2
作者：
Billington, SJ;Jost, BH;Songer, JG
通讯作者：
Songer, JG
影响因子：
64.5
作者：
Gurcel, Laure;Abrami, Laurence;van der Goot, F. Gisou
通讯作者：
van der Goot, F. Gisou
影响因子：
4.6
作者：
Griffin S;Preta G;Sheldon IM
通讯作者：
Sheldon IM