Mitochondrial requirement for endothelial responses to cyclic strain: implications for mechanotransduction

Ali, Mir H.; Pearlstein, Daryl P.; Mathieu, Carol; Schumacker, Paul T.

doi:10.1152/ajplung.00389.2003

Cited by 139 publications

(127 citation statements)

References 57 publications

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“…1A). Previously, hypoxia and mechanical stretch were also found to increase mitochondrial production of ROS (1,6), and increased ROS were found to trigger cellular responses (1, 6), analogous to the responses found in the present studies. Fig.…”

Section: Discussionsupporting

confidence: 88%

Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP

Zhou¹,

Ferraris²,

Burg³

2006

American Journal of Physiology-Renal Physiology

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Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP. Am J Physiol Renal Physiol 290: F1169 -F1176, 2006. First published November 22, 2005 doi:10.1152/ajprenal.00378.2005.-Hypertonicity activates the transcription factor tonicity-responsive enhancer/ osmotic response element binding protein (TonEBP/OREBP), resulting in increased expression of genes involved in osmoprotective accumulation of organic osmolytes, including glycine betaine, and in increased expression of osmoprotective heat shock proteins. Our previous studies showed that high NaCl increases reactive oxygen species (ROS), which contribute to activation of TonEBP/OREBP. Mitochondria are a major source of ROS. The purpose of the present study was to examine whether mitochondria produce the ROS that contribute to activation of TonEBP/OREBP. We inhibited mitochondrial ROS production in HEK293 cells with rotenone and myxothiazol, which inhibit mitochondrial complexes I and III, respectively. Rotenone (250 nM) and myxothiazol (12 nM) reduce high NaClinduced ROS over 40%, whereas apocynin (100 M), an inhibitor of NADPH oxidase, and allopurinol (100 M), an inhibitor of xanthine oxidase, have no significant effect. Rotenone and myxothiazol reduce high NaCl-induced increases in TonEBP/OREBP transcriptional activity (ORE/TonE reporter assay) and BGT1 (betaine transporter) mRNA abundance ranging from 53 to 69%. They inhibit high NaClinduced TonEBP/OREBP transactivating activity, but not its nuclear translocation. Release of ATP into the medium on hypertonic stress has been proposed to be a signal that triggers cellular osmotic responses. However, we do not detect release of ATP into the medium or inhibition of high NaCl-induced ORE/TonE reporter activity by an ATPase, apyrase (20 U/ml), indicating that high NaCl-induced activation of TonEBP/OREBP is not mediated by release of ATP. We conclude that high NaCl increases mitochondrial ROS production, which contributes to the activation of TonEBP/OREBP by increasing its transactivating activity. superoxides; rotenone; myxothiazol; transactivation; nuclear translocation; ATP release THE TRANSCRIPTION FACTOR tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/OREBP), when activated by high NaCl and other hypertonic stresses, increases transcription of genes involved in osmoprotective accumulation of organic osmolytes, including glycine betaine and heat shock proteins (26,34,48). In the kidney, TonEBP/ OREBP also controls expression of a urea transporter (UT-A) (36) and of aquaporin-2 (22, 26), thus regulating the urinary concentrating mechanism. Hypertonicity, induced by high NaCl, increases reactive oxygen species (ROS) in mIMCD3 (50), mIMCD-K2 (49), HEK293 cells (51), and, presumably, also in the renal medulla, where interstitial NaCl normally is high and there is oxidative stress that results in protein carbonylation (50). We previously found that high NaCl-induced ROS contribute to activation of TonEBP/OREBP (51). The p...

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Section: Discussionsupporting

confidence: 88%

Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP

Zhou¹,

Ferraris²,

Burg³

2006

American Journal of Physiology-Renal Physiology

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“…Supporting our findings, Yun et al (47) observed a threefold increase in monocyte adhesion to cyclically strained HUVEC (25% strain, 0.5 Hz); antibodies against ICAM or VCAM decreased the monocyte adhesion (46). Ali et al (1) found that cyclic strain (ϳ25%, 0.25 Hz, 6 h) induced VCAM-1 and ICAM-1 expression 5.5-fold and 2.2-fold, respectively, in HUVEC, which was attenuated by DPI. The opposite H 2 O 2 profiles, enzyme activities, and cell adhesion molecule expressions between HAEC and HUVEC in response to cyclic strain and motion control provided evidence that ECs discriminate different mechanical stimuli and that the resulting phenotypes are specific to EC type.…”

Section: Discussionmentioning

confidence: 99%

“…Cyclic strain studies of cultured EC have been shown to increase ROS production (1,20,21,31,45). Microarray studies of EC subjected to cyclic strain showed that most differentially expressed genes are associated with oxidative stress (14).…”

mentioning

confidence: 99%

Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types

Sung

Yee²,

Eskin³

et al. 2007

American Journal of Physiology-Cell Physiology

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Sung H-J, Yee A, Eskin SG, McIntire LV. Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types. Am J Physiol Cell Physiol 293: C87-C94, 2007. First published February 21, 2007 doi:10.1152/ajpcell.00585.2006.-The phenotype of endothelial cells (ECs) is specific to the vascular bed from which they originate. To examine how mechanical forces alter the phenotype of different ECs, we compared the effects of cyclic strain and motion control on reactive oxygen species (ROS) production and metabolism and cell adhesion molecule expression in human umbilical vein endothelial cells (HUVEC) vs. human aortic endothelial cells (HAEC). HUVEC and HAEC were subjected to cyclic strain (10% or 20%, 1 Hz), to a motion control that simulated fluid agitation over the cells without strain, or to static conditions for 24 h. We measured H2O2 production with dichlorodihydrofluorescein acetate and superoxide with dihydroethidium fluorescence changes; superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities spectrophotometrically; and vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 protein expression with Western blot analyses. HUVEC under cyclic strain showed 1) higher intracellular H2O2 levels, 2) increased SOD, catalase, and GPx activities, and 3) greater VCAM-1 and ICAM-1 protein expression, compared with motion control or static conditions. However, in HAEC, motion control induced higher levels of ROS, enzyme activities associated with ROS defense, and VCAM-1 and ICAM-1 expression than cyclic strain. The opposite responses obtained with these two human EC types may reflect their vessels of origin, in that HAEC are subjected to higher cyclic strain deformations in vivo than HUVEC.

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“…This triggers a stimulus for the production of free radicals that, among other intracellular effects, promotes P-selectin exocytosis and increases the production of vascular cell adhesion molecule via nuclear factor kappa B (NF-κB), as well as proinflammatory events, which facilitate leukocyte adhesion. (57,58) In summary, the hyperdistension of the lung parenchyma in VILI seems to be transmitted from the extracellular environment to the interior of the cells through the extracellular matrixcytoskeleton connection, in which integrin plays the role of mediator. In this mechanism, certain intracellular proteins associated with adhesion structures are important, especially FAK and paxillin.…”

Section: Cell-matrix Interaction and Mechanotransductionmentioning

confidence: 99%

Citoesqueleto e mecanotransdução na fisiopatologia da lesão pulmonar induzida por ventilador

Taniguchi¹,

Caldini

Velasco

et al. 2010

J. bras. pneumol.

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Although mechanical ventilation is an important therapy, it can result in complications. One major complication is ventilator-induced lung injury, which is caused by alveolar hyperdistension, leading to an inflammatory process, with neutrophilic infiltration, hyaline membrane formation, fibrogenesis and impaired gas exchange. In this process, cellular mechanotransduction of the overstretching stimulus is mediated by means of the cytoskeleton and its cell-cell and cell-extracellular matrix interactions, in such a way that the mechanical stimulus of ventilation is translated into an intracellular biochemical signal, inducing endothelial activation, pulmonary vascular permeability, leukocyte chemotaxis, cytokine production and, possibly, distal organ failure. Clinical studies have shown the relationship between pulmonary distension and mortality in patients with ventilator-induced lung injury. However, although the cytoskeleton plays a fundamental role in the pathogenesis of ventilator-induced lung injury, there have been few in vivo studies of alterations in the cytoskeleton and in cytoskeleton-associated proteins during this pathological process.Keywords: Respiration, artificial; Cytoskeleton; Cell adhesion molecules; Focal adhesions; Mechanotransduction, cellular. ResumoA ventilação mecânica é uma terapia importante, mas pode resultar em complicações. Uma das mais relevantes é a lesão pulmonar induzida por ventilador. Devido à hiperdistensão alveolar, o pulmão inicia um processo inflamatório, com infiltrado neutrofílico, formação de membrana hialina, fibrogênese e prejuízo de troca gasosa. Nesse processo, a mecanotransdução da hiperdistensão celular é mediada através do citoesqueleto da célula e de suas interações com a matriz extracelular e com as células vizinhas, de modo que o estímulo mecânico da ventilação se traduz em sinalização bioquímica intracelular, desencadeando ativação endotelial, permeabilidade vascular pulmonar, quimiotaxia leucocitária, produção de citocinas e, possivelmente, lesão de órgãos à distância. Estudos clínicos demonstram essa relação entre distensão pulmonar e mortalidade em pacientes com lesão pulmonar induzida por ventilador. Entretanto, apesar de o citoesqueleto ter um papel fundamental na patogênese da lesão pulmonar induzida por ventilador, a literatura carece de estudos utilizando modelos in vivo sobre as alterações do citoesqueleto e de suas proteínas associadas durante esse processo patológico. Subsequent studies focused on the mechanical factors that triggered VILI, such as peak inspiratory pressure and V T .(9-12) Dreyfuss et al. confirmed the findings of Webb and Tierney and demonstrated that V T was the major determinant of alveolar injury and alveolocapillary membrane injury, which gave rise to the term "volutrauma". (13,14) In an important study, they compared rats ventilated with high V T and negative pressure (through a negative pressure ventilator, known as iron lung) with rats ventilated with high pressure and low V T (with thoracoabdominal movement restricte...

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Mitochondrial requirement for endothelial responses to cyclic strain: implications for mechanotransduction

Cited by 139 publications

References 57 publications

Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP

Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP

Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types

Citoesqueleto e mecanotransdução na fisiopatologia da lesão pulmonar induzida por ventilador

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