ΔMST and the Regulation of Cardiac CSE and OTR Expression in Trauma and Hemorrhage.

Britta Trautwein,Tamara Merz,Peter Radermacher,Csaba Szabo,Enrico Calzia,Nicole Denoix,Oscar Mccook

doi:10.3390/antiox10020233

Britta Trautwein, Tamara Merz + Show 5 more

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https://doi.org/10.3390/antiox10020233

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Abstract

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 (H2S) 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 H2S and OT are not clear, but they point the way to potential cardioprotective therapies.

Highlights

IntroductionThe neuroendocrine oxytocin (OT) system and the gasotransmitter hydrogen sulfide (H2 S), endogenously produced by cystathionine β-lyase (CSE), cystathionine γ-synthase (CBS), and 3-mercaptopyruvate-sulfurtransferase (MST), have been shown to have parallel roles in the heart in response to trauma
Hemorrhagic shock (HS) and HS + Txt significantly reduced expression of cardiac cystathionine β-lyase (CSE) and oxytocin receptor (OTR) compared to naïve animals. ∆MST animals had significantly lower CSE and OTR expression already in the naive state, and no further reduction in MST expression after injury was observed
In a clinically relevant, resuscitated mouse model, naive and injured ∆MST mice had a reduction of cardiac CSE and OTR expression

Summary

Introduction

The neuroendocrine oxytocin (OT) system and the gasotransmitter hydrogen sulfide (H2 S), endogenously produced by cystathionine β-lyase (CSE), cystathionine γ-synthase (CBS), and 3-mercaptopyruvate-sulfurtransferase (MST), have been shown to have parallel roles in the heart in response to trauma. OT and H2 S are relevant in models of both psychological and physical trauma, displaying cardio-protective effects [1]. Genetic deletion (ko) of MST has resulted in hypertension and cardiac hypertrophy, at least in aged mice [2]; it has been associated with increased anxietylike behaviors [3]. We investigated the effects of a genetic MST mutation (∆MST) in a resuscitated mouse model of traumatic-hemorrhagic shock, and found no significant differences in hemodynamics, gas exchange, metabolism, acid base status, or survival between ∆MST and the respective wild type groups [4]

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