Activity of cytosolic aconitase.

<p>Activity of cytosolic aconitase.</p

Infarct sizes of the rat hearts after exposure to the different experimental protocols.

<p>Data are presented as Mean ± SEM.* p < 0.05 versus I/R.</p

Experimental protocols.

<p>Experimental protocols.</p

The Methionine-Centered Redox Cycle.

<p>The formation of methionine sulfoxide (MetO) can result from the oxidation of free methionine, or a methionyl residue of a protein. Additional oxidation will generate methionine sulfone (MetO₂), a product that is almost irreversible in biological systems, and can cause protein denaturation. MetO can be reduced by methionine sulfoxide reductases (MsrA or MsrB isoform), through thioredoxin (Trx). Thioredoxin reductase (TrxR) regenerates the oxidized Trx (Trx_ox) via critical components of the cellular redox system, NADP/NADP(H) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159951#pone.0159951.ref032" target="_blank">32</a>].</p

The Loss of Myocardial Benefit following Ischemic Preconditioning Is Associated with Dysregulation of Iron Homeostasis in Diet-Induced Diabetes - Fig 1

<p><b>Three basic experimental protocols (A) and post-ischemic recovery of the WI (B and C).</b> (A) (i) IPC followed by I/R (upper bar); ii) I/R (middle bar); and (iii) continuous perfusion (lower bar). (B and C) Post-ischemic recovery of WI for hearts from Cohen diabetes-resistant (CDr) rats (Panel 1B) and Cohen diabetes-sensitive rats (CDs) (Panel 1C), subjected to I/R without and with prior IPC. Animals were fed on either high sucrose/low copper diet (HSD) or regular (RD) diets. WI was calculated as the product of the Developed Pressure x Heart Rate (DP*HR). The degree of cardioprotection was expressed by as percent (%) ratio of two values: WI at the 120^th minute (completion of the reperfusion phase) and WI at 10^th minute (the last minute of the stabilization phase). Mean ± SEM values are shown; <b>*</b>—p<0.05 in IPC+I/R <i>versus</i> I/R in CDs-RD; ^<b>#</b>—p<0.05 in IPC+I/R <i>versus</i> I/R in CDr-HSD; ^<b>‡</b>—p<0.05 in IPC+I/R <i>versus</i> I/R in CDr-RD.</p

The Loss of Myocardial Benefit following Ischemic Preconditioning Is Associated with Dysregulation of Iron Homeostasis in Diet-Induced Diabetes

<div><p>Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the non-diabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders.</p></div

Activities of methionine sulfoxide reductase.

<p>Activities of methionine sulfoxide reductase.</p

Hemodynamic parameters of the rat hearts after exposure to the different experimental protocols.

<p>Hemodynamic parameters of the rat hearts after exposure to the different experimental protocols.</p

Ferritin and iron content at various times of the perfusion protocol.

<p>Ferritin and iron content at various times of the perfusion protocol.</p

Thioredoxin and thioredoxin-reductase protein levels.

<p>Thioredoxin and thioredoxin-reductase protein levels.</p