Increased production of reactive oxygen species contributes to the etiology of diabetes complications. Pathophysiological stimuli that increase oxidative stress upregulate heme oxygenase (HO)-1, a cytoprotective heme-degrading enzyme. We hypothesized that HO-1 may be important in myocardial injury that is exacerbated by diabetes. To test this hypothesis, the left anterior descending coronary arteries of nondiabetic and diabetic wild-type (HO-1 ؉/؉ ) and HO-1 null (HO-1 -/-) mice were ligated for 1 h followed by 24 h reperfusion. C oronary artery disease leading to myocardial infarction and heart failure is a chronic complication of diabetes, accounting for Ͼ75% of hospitalizations in diabetic patients (1-3). In addition, myocardial infarction accounts for nearly 50% of all deaths in patients with diabetes (4). The mortality rate of diabetic patients after acute myocardial infarction resulting from ischemia/reperfusion injury is approximately twice that of nondiabetic patients (5-7).Several reports have suggested that increased oxidative stress contributes to the development and progression of diabetes complications (8 -10). Heme oxygenase (HO)-1, the inducible isoform of the HO family of proteins, is induced by a variety of stimuli that increase oxidative stress (11,12). By degrading the oxidant heme and generating the antioxidant bilirubin and anti-inflammatory molecule carbon monoxide (CO), HO-1 protects cells from death due to pathophysiological stress and oxidative injury (13-18). In diseases that are initiated by stress, such as atherosclerotic lesion formation and vascular remodeling, lack of endogenous HO-1 exacerbates lesion formation (19). Given its cytoprotective role in many cell types and organs, there is growing interest in the role of HO-1 in diabetes (20 -23). HO-1 protects islet cells from apoptosis and improves in vivo function after transplantation (20). HO-1 also protects diabetic rats from endothelial cell dysfunction by preventing endothelial cell sloughing (24).Myocardial ischemia/reperfusion injury results in greater damage in the diabetic (db/db) mouse hearts than nondiabetic controls (25). While Nishio et al. (26) reported HO-1 induction in diabetic rat hearts, the functional role of HO-1 in diabetes complications of myocardial infarction has not been examined. We have shown that in response to hypoxia, which leads to pulmonary hypertension, HO-1 null (HO-1 -/-) mice develop severe right ventricular dilatation and infarction due to oxidative damage (13). This prior study demonstrated the detrimental consequences of HO-1 deficiency in the heart in response to pathological stress. HO-1 has a critical role in cardiac homeostasis in response to oxidative stress-induced injury (16,18,27) and that hyperglycemia increases the production of reactive oxygen species in diabetes (28,29). We hypothesized that in the absence of HO-1, cardiomyocytes may be more susceptible to ischemia/reperfusion damage and diabetes may exacerbate the myocardial injury. To test our hypothesis in vivo, we induced diabe...

Immunoreactivity for V-1L can be used as a synaptic marker for early changes before more severe neurodegenerative events. The present results suggest that estrogen protects neurons in the GCL including RGCs from both apoptosis and early changes in synaptic connections associated with ischemia and potentially preceding apoptosis.

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Purposely strengthening masticatory muscle movement during the denervated atrophic stage of the masseter can prolong the duration of masseter rehypertrophy.

The differential distribution of IP3Rs is used by rod bipolar cells to convey Ca2+ signals that are distinct in their duration, amplitude, and kinetics at the subcellular level, and that serve the functions of individual subcellular compartments. IP3R-mediated Ca2+ signaling indicates a potential mechanism for the adaptation of the ON-pathway of vision and for coincidence and threshold detection in retinal neurons.