Regulation of NAD(P)H Oxidase by Associated Protein Disulfide Isomerase in Vascular Smooth Muscle Cells

Janiszewski, Mariano; Lopes, Lucia Rossetti; Carmo, Alípio O.; Pedro, Marcelo A.; Brandes, Ralf P.; Santos, Célio X.C.; Laurindo, Francisco Rafael Martins

doi:10.1074/jbc.m509255200

Cited by 206 publications

(188 citation statements)

References 56 publications

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“…Some of these proteins were: prohibitin, which plays a role in regulating proliferation and inhibits DNA synthesis (25), Forkhead box P4 isoform 1, which is a transcriptional repressor that has been involved in cardiac morphogenesis (26), and protein disulfide isomerase-associated 3, which is classified as a signal transduction protein, but which could also be classified as an electron transport protein and plays a role in the oxidative process (27).…”

Section: Resultsmentioning

confidence: 99%

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

Teixeira

Iwai

Kuramoto

et al. 2006

Braz J Med Biol Res

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Chronic Chagas' disease cardiomyopathy (CCC) is an often fatal outcome of Trypanosoma cruzi infection, with a poorer prognosis than other cardiomyopathies. CCC is refractory to heart failure treatments, and is the major indication of heart transplantation in Latin America. A diffuse myocarditis, plus intense myocardial hypertrophy, damage and fibrosis, in the presence of very few T. cruzi forms, are the histopathological hallmarks of CCC. To gain a better understanding of the pathophysiology of CCC, we analyzed the protein profile in the affected CCC myocardium. Homogenates from left ventricular myocardial samples of end-stage CCC hearts explanted during heart transplantation were subjected to two-dimensional electrophoresis with Coomassie blue staining; protein identification was performed by MALDI-ToF mass spectrometry and peptide mass fingerprinting. The identification of selected proteins was confirmed by immunoblotting. We demonstrated that 246 proteins matched in gels from two CCC patients. They corresponded to 112 distinct proteins. Along with structural/contractile and metabolism proteins, we also identified proteins involved in apoptosis (caspase 8, caspase 2), immune system (T cell receptor ß chain, granzyme A, HLA class I) and stress processes (heat shock proteins, superoxide dismutases, and other oxidative stress proteins). Proteins involved in cell signaling and transcriptional factors were also identified. The identification of caspases and oxidative stress proteins suggests the occurrence of active apoptosis and significant oxidative stress in CCC myocardium. These results generated an inventory of myocardial proteins in CCC that should contribute to the generation of hypothesis-driven experiments designed on the basis of the classes of proteins identified here.

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Section: Resultsmentioning

confidence: 99%

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

Teixeira

Iwai

Kuramoto

et al. 2006

Braz J Med Biol Res

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“…H 2 O 2 levels were detected with a homovanillic acid assay (22). EPR was used to measure O 2 − generation by heart particulate fractions, using a 5,5-dimethylpyrroline-N-oxide (DMPO, 50 mmol/L) spin trap (40).…”

Section: Methodsmentioning

confidence: 99%

NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis

Zhang

Brewer

Schröder

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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399

428

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Cardiac failure occurs when the heart fails to adapt to chronic stresses. Reactive oxygen species (ROS)-dependent signaling is implicated in cardiac stress responses, but the role of different ROS sources remains unclear. Here we report that NADPH oxidase-4 (Nox4) facilitates cardiac adaptation to chronic stress. Unlike other Nox proteins, Nox4 activity is regulated mainly by its expression level, which increases in cardiomyocytes under stresses such as pressure overload or hypoxia. To investigate the functional role of Nox4 during the cardiac response to stress, we generated mice with a genetic deletion of Nox4 or a cardiomyocyte-targeted overexpression of Nox4. Basal cardiac function was normal in both models, but Nox4-null animals developed exaggerated contractile dysfunction, hypertrophy, and cardiac dilatation during exposure to chronic overload whereas Nox4-transgenic mice were protected. Investigation of mechanisms underlying this protective effect revealed a significant Nox4-dependent preservation of myocardial capillary density after pressure overload. Nox4 enhanced stress-induced activation of cardiomyocyte hypoxia inducible factor 1 and the release of vascular endothelial growth factor, resulting in increased paracrine angiogenic activity. These data indicate that cardiomyocyte Nox4 is a unique inducible regulator of myocardial angiogenesis, a key determinant of cardiac adaptation to overload stress. Our results also have wider relevance to the use of nonspecific antioxidant approaches in cardiac disease and may provide an explanation for the failure of such strategies in many settings.cardiac remodeling | hypoxia inducible factor | reactive oxygen species

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“…[54][55][56][57][58][59][60] Ang II promotes ROS production by the activation of membrane-bound NAD(P)H oxidase. 54,57,59 This activation was first demonstrated by Griendling et al 59 in vascular smooth muscle cells.…”

Section: Endothelial Dysfunction and Oxidative Stress In The Etiologymentioning

confidence: 99%

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

2010

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The renin-angiotensin-aldosterone system (RAAS) is a pivotal regulator of physiological homeostasis and diseases of the cardiovascular system. Recently, new factors have been discovered, such as angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas. This newly defined ACE2-angiotensin-(1-7)-Mas axis was shown to have a critical role in the vasculature and in the heart, exerting mainly protective effects. One important mechanism of the classic and the new RAAS regulate vascular function is through the regulation of redox signaling. Angiotensin II is a classic prooxidant peptide that increases superoxide production through the activation of NAD(P)H oxidases. This review summarizes the current knowledge about the ACE2-angiotensin-(1-7)-Mas axis and redox signaling in the context of cardiovascular regulation and disease. By interacting with its receptor Mas, angiotensin-(1-7) induces the release of nitric oxide from endothelial cells and thereby counteracts the effects of angiotensin II. ACE2 converts angiotensin II to angiotensin-(1-7) and, thus, is a pivotal regulator of the local effects of the RAAS on the vessel wall. Taken together, the ACE2-angiotensin-(1-7)-Mas axis emerges as a novel therapeutic target in the context of cardiovascular and metabolic diseases.

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Regulation of NAD(P)H Oxidase by Associated Protein Disulfide Isomerase in Vascular Smooth Muscle Cells

Cited by 206 publications

References 56 publications

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

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