Trautwein Britta, Merz Tamara, Denoix Nicole, Szabo Csaba, Calzia Enrico, Radermacher Peter, McCook Oscar
Institute for Anesthesiological Pathophysiology and Process Engineering, Ulm University Medical Center, 89081 Um, Germany.
Clinic for Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, 89070 Ulm, Germany.
Antioxidants (Basel). 2021 Feb 3;10(2):233. doi: 10.3390/antiox10020233.
Genetic deletion of 3-mercaptopyruvate sulfurtransferase (MST) is known to result in hypertension and cardiac hypertrophy in older mice, and is associated with increased anxiety-like behaviors. Endogenous hydrogen sulfide (HS) produced by MST in the mitochondria is also known to be involved in physiological and cellular bioenergetics, and its dysfunction associated with depressive behavior and increased cardiovascular morbidity. Interestingly, early life stress has been shown to lead to a significant loss of cystathionine-γ-lyase (CSE) and oxytocin receptor (OTR) expression in the heart. Thus, we were interested in testing the hypothesis of whether genetic MST mutation (ΔMST) would affect cardiac CSE and OTR expression and affect the mitochondrial respiration in a clinically relevant, resuscitated, mouse model of trauma and hemorrhagic shock. In ΔMST mice, we found a reduction of CSE and OTR in both the naive as well as injured state, in contrast to the wild type (wt) controls. Interestingly, the ΔMST showed a different complex IV response to injury than the wt controls, although our claims are based on the non-demonstrated assumption that naive wt and naive ΔMST mice have comparable complex IV activity. Finally, hemorrhagic shock led to a reduction of CSE and OTR, confirming previous results in the injured mouse heart. To date, the exact mechanisms of the cardiac interaction between HS and OT are not clear, but they point the way to potential cardioprotective therapies.
已知基因敲除3-巯基丙酮酸硫转移酶（MST）会导致老年小鼠出现高血压和心脏肥大，并与焦虑样行为增加有关。线粒体中由MST产生的内源性硫化氢（HS）也参与生理和细胞生物能量代谢，其功能障碍与抑郁行为和心血管发病率增加有关。有趣的是，早年应激已被证明会导致心脏中胱硫醚-γ-裂解酶（CSE）和催产素受体（OTR）表达显著丧失。因此，我们有兴趣测试基因MST突变（ΔMST）是否会影响心脏CSE和OTR表达，并在临床相关的复苏创伤和失血性休克小鼠模型中影响线粒体呼吸这一假设。在ΔMST小鼠中，我们发现无论是在未受伤状态还是受伤状态下，与野生型（wt）对照相比，CSE和OTR均减少。有趣的是，尽管我们的结论基于未证实的假设，即未受伤的wt小鼠和未受伤的ΔMST小鼠具有相当的复合物IV活性，但ΔMST对损伤的复合物IV反应与wt对照不同。最后，失血性休克导致CSE和OTR减少，证实了先前在受伤小鼠心脏中的研究结果。迄今为止，HS和OT之间心脏相互作用的确切机制尚不清楚，但它们为潜在的心脏保护疗法指明了方向。
