Contractile response of norepinephrine is modulated by caspase-3 in adult rat ventricular myocytes isolated from septic rat heart.
Contractile response of norepinephrine is modulated by caspase-3 in adult rat ventricular myocytes isolated from septic rat heart.
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DOI：
10.1016/j.phrs.2009.04.009
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发表时间：
2009-10
影响因子：
9.3
通讯作者：
Sharma, Avadhesh C.
中科院分区：
文献类型：
--
作者：
Chopra, Mani;Sharma, Avadhesh C.
脓毒症占重症监护病房因心功能障碍死亡的 50%。脓毒症期间去甲肾上腺素 (NE) 的细胞机制尚不清楚。使用脓毒症成年大鼠心室肌细胞 (ARVM) 范例，我们检查了 NE 收缩反应减弱的分子机制。我们测试了以下假设：NE 诱导的活性 caspase-3 增加会导致脓毒症诱导的 ARVM 收缩功能障碍。从假手术和脓毒症雄性大鼠采集的心脏中分离出单个 ARVM。在使用和不使用 QVD-OPH、哌唑嗪和阿替洛尔的 NE 处理的 ARVM 中测定了 caspase-3 级联蛋白的收缩特性和表达，以表征 NE对其机械特性的影响。与假 ARVM 相比，脓毒症 ARVM 的峰值缩短 (PS) 显着降低。与脓毒症 ARVM 相比，NE 对假 ARVM PS 的影响更为明显，表明 NE 的收缩反应减弱。 QVD-OPH 存在下的 NE 改善了 18 小时时脓毒症引起的 PS 下降，但在 1 小时没有改善，而 NE 对脓毒症引起的收缩反应的影响在 18 小时时仍不受哌唑嗪和阿替洛尔的影响。 QVD-OPH 逆转了 NE 处理的脓毒症 ARVM 中 caspase-3 表达的上调，如显示 caspase-3 荧光的脓毒症 ARVM 数量增加所示。使用 caspase-3 siRNA 转染 ARVM 可阻断脓毒症诱导的 caspase-3 上调，并在 NE 治疗后增加 PS。这些数据表明，caspase-3 抑制改善了脓毒症引起的 ARVM 收缩性下降，并阻断了 NE 减弱的收缩反应。
Sepsis accounts for 50% of intensive care unit deaths due to cardiac dysfunction. The cellular mechanisms following norepinephrine (NE) during sepsis are undefined. Using a septic adult rat ventricular myocyte (ARVM) paradigm, we examined the molecular mechanism responsible for the blunted contractile response of NE. We tested the hypothesis that NE-induced increases in active caspase-3 contribute to sepsis-induced ARVM contractile dysfunction. Single ARVMs were isolated from hearts harvested from sham and septic male rats. The contractile properties and expression of caspase-3 cascade proteins were determined in ARVMs treated with NE with and without QVD-OPH, prazosin and atenolol to characterize the effect of NE on their mechanical properties. Septic ARVMs exhibited a significant decrease in peak shortening (PS) compared to sham ARVMs. The effect of NE on the PS of the sham ARVMs was more pronounced compared to the septic ARVMs, suggesting a blunted contractile response of NE. NE in the presence of QVD-OPH ameliorated the sepsis-induced decrease in PS at 18h but not at 1h, while the effect of NE on sepsis-induced contractile response remained unaffected at 18h by prazosin and atenolol. An upregulated expression of caspase-3 in NE-treated septic ARVMs was reversed by QVD-OPH, as seen by the increased number of septic ARVMs exhibiting caspase-3 fluorescence. Transfection of ARVMs using caspase-3 siRNA blocked sepsis-induced upregulation of caspase-3 and increased PS following NE treatment. These data suggest that caspase-3 inhibition ameliorated sepsis-induced decreased ARVM contractility and blocked the blunted contractile response of NE.
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影响因子：
5
作者：
Gupta, A;Aberle, NS;Sharma, AC
通讯作者：
Sharma, AC
影响因子：
38.9
作者：
Rabuel, C.;Mebazaa, A.
通讯作者：
Mebazaa, A.
影响因子：
3.3
作者：
Carlson, Deborah L.;Maass, David L.;Horton, Jureta W.
通讯作者：
Horton, Jureta W.
影响因子：
37.8
作者：
Chang, J;Wei, L;Schwartz, RJ
通讯作者：
Schwartz, RJ
DOI：
10.1073/pnas.092022999
发表时间：
2002-04-30
影响因子：
11.1
作者：
Communal, C;Sumandea, M;Hajjar, RJ
通讯作者：
Hajjar, RJ