Abstract
Mitochondrial permeability transition pores (mPTPs) have become an important topic in investigating the initiation and signaling pathways involved in cardioprotection. Experimental streptozotocin-induced diabetes mellitus (D) was shown to provide sufficient protection to the myocardium via compensatory mechanisms enabling mitochondria to produce energy under pathological conditions during the acute phase. The hypothesized involvement of mPTPs in these processes prompted us to use liquid chromatography and mass spectrometry-based proteomic analysis to investigate the effects of the acute-phase D condition on the structural and regulatory components of this multienzyme complex and the changes caused by compensation events. We detected ADT1, ATP5H, ATPA, and ATPB as the most abundant mPTP proteins. The between-group differences in protein abundance of the mPTP complex as a whole were significantly upregulated in the D group when compared with the control (C) group (p = 0.0106), but fold changes in individual protein expression levels were not significantly altered except for ATP5H, ATP5J, and KCRS. However, none of them passed the criterion of a 1.5-fold change in differential expression for biologically meaningful change. Visualization of the (dis-)similarity between the C and D groups and pairwise correlations revealed different patterns of protein interactions under the C and D conditions which may be linked to endogenous protective processes, of which beneficial effects on myocardial function were previously confirmed.
Highlights
Ischemic heart disease remains the leading cause of morbidity and mortality worldwide, mechanisms leading to cardioprotection are becoming a growing research issue
Besides changes in the abundance of a single feature in the MS data, we are often interested in comparing the abundances of a potentially large number of features that are simultaneously detected as part of the experiment
Cardioprotection includes all methods and mechanisms that lead to a reduction in infarct size and a reduction in the risk of post-ischemic heart failure
Summary
Ischemic heart disease remains the leading cause of morbidity and mortality worldwide, mechanisms leading to cardioprotection are becoming a growing research issue. As a cardioprotective strategy for decreasing the vulnerability of the myocardium to ischemia/reperfusion (I/R) injury, ischemic preconditioning (PC) has received great attention for its potent infarct size-limiting effect in experiments using healthy animals [1,2]. Myocardial protection by PC is achieved by the activation of multiple protective signaling pathways hypothesized to inhibit mitochondrial permeability transition pore (mPTP) opening upon reperfusion [6,7,8,9,10]. The pores are primarily formed and opened upon an increase in Ca2+ in the mitochondrial matrix, signaling by reactive oxygen species (ROS) or inorganic phosphates, or intracellular acidification [8,11,12,13,14]
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