Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of oxidative stress.

Background: Animal studies suggest that reactive oxygen species (ROS) play an important role in the development of diabetic cardiomyopathy.

Hypothesis: Matrix metalloproteinase-2 (MMP-2) is activated by ROS and contributes to the acute loss of myocardial contractile function by targeting and cleaving susceptible proteins including troponin I (TnI) and alpha-actinin.

Methods: Using the streptozotocin-induced diabetic rat model, we evaluated the effect of daily in vivo administration of sodium selenate (0.

Antioxidants but not doxycycline treatments restore depressed beta-adrenergic responses of the heart in diabetic rats.

Reactive oxygen species (ROS) play important roles in the development of diabetic cardiomyopathy. Matrix metalloproteinases (MMPs) can get activated by ROS and contribute to loss of myocardial contractile function in oxidative stress injury. Previously we have shown that either a MMP-2 inhibitor doxycycline or an antioxidant selenium treatment in vivo prevented diabetes-induced cardiac dysfunction significantly.

Protective action of doxycycline against diabetic cardiomyopathy in rats.

Background And Purpose: Reactive oxygen and nitrogen species play an important role in the development of diabetic cardiomyopathy. They can activate matrix metalloproteinases (MMPs), and MMP-2 in particular is known to mediate early consequences of oxidative stress injury in the heart. Therefore, we investigated the role of MMP-2 and the effect of the MMP inhibitor doxycycline on the changes of heart function caused by diabetes.

Selenium inhibits proliferation signaling and restores sodium/potassium pump function of diabetic rat aorta.

Diabetes is characterized with increased oxidant stress, vasculopathy, and neuropathy. In diabetic vasculopathy, the observed thickening of the media and intima is not only a result of vascular smooth muscle cell proliferation but also due to modification of the extracellular matrix by these cells. Also, there is hampered membrane function and a reduction in sodium pump expression in the vessels of the diabetic animals.

Ouabain-induced signaling and vascular smooth muscle cell proliferation.

The hypothesis of this study is that the sodium pump complex acts as an intracellular signal-transducing molecule in canine vascular smooth muscle cells through its interaction with other membrane and cytoskeletal proteins. We have demonstrated that 1 nm ouabain induced transactivation of the epidermal growth factor receptor (EGFR), resulting in increased proliferation and bromodeoxyuridine (BrdUrd) uptake. Immunoprecipitation and Western blotting showed that the EGFR and Src were phosphorylated within 5 min of 10(-9) m ouabain stimulation.