Heme Oxygenase-1 Attenuates Glucose-Mediated Cell Growth Arrest and Apoptosis in Human Microvessel Endothelial Cells

Abraham, Nader G.; Kushida, Taketoshi; McClung, J. A.; Weiss, Melvin B.; Quan, Shuo; Lafaro, Rocky; Darzynkiewicz, Zbigniew; Wolin, Michael S.

doi:10.1161/01.res.0000091828.36599.34

Cited by 140 publications

(147 citation statements)

References 54 publications

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“…42 HO-1 attenuates glucose-mediated cell growth arrest and apoptosis in human micro-vessel endothelial cells. 43 These may explain why mice pretreated with RvD1 showed higher expression of HO-1 and TJ proteins and decrease of apoptosis cells in TUNEL compared with the LPS group in this study. Moreover, pro-injected with Znpp mice showed more positive cells in TUNEL section compared with LPS þ RvD1 group, but the apoptosis cells in the LPS group proved no marked difference with the LPS þ Znpp group.…”

Section: Rvd1 Reduces Deterioration Of Tj Proteins W Xie Et Almentioning

confidence: 70%

Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1 in LPS-induced mice

Xie

Wang

et al. 2013

Laboratory Investigation

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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary permeability with high mortality. Resolvin D1 (RvD1), which has potent anti-inflammatory and pro-resolving activity, can attenuate pulmonary edema in the animal model of ALI. However, the mechanism underlying the protection of RvD1 on pulmonary edema is still unknown. Here we explore the effects and mechanism of RvD1 on the disruption of tight junction protein that results in the permeability edema in a model of lipopolysaccharide (LPS)-induced ALI. The severity of pulmonary edema was assessed by wet-to-dry rate and Evans blue infiltration; expressions of tight junction (TJ) proteins occludin and zona occludin-1 (ZO-1) were examined by immunofluorescence staining and western blot; mRNA in lung tissue was studied by real time-PCR; the TUNEL kit was performed for the detection of apoptosis of pulmonary barrier. Twenty-four hours after LPS inhalation by mice, wet-to-dry rate and Evans blue infiltration indicated that pretreatment with RvD1 relieved the pulmonary edema and pulmonary capillary permeability. Moreover, RvD1 attenuated the LPS-induced deterioration of TJ protein ZO-1 and occludin significantly. And we found that RvD1 increased heme oxygenase-1 (HO-1) expression contributed to the protection on the deterioration of TJs. In addition, we found that RvD1 could reduce pulmonary cellular apoptosis in LPS-induced mice. In conclusion, RvD1 possesses the ability that relieves the pulmonary edema and restores pulmonary capillary permeability and reduces disruption of TJs in LPS-induced ALI of mice, at least in part, by upregulating HO-1 expression.

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Section: Rvd1 Reduces Deterioration Of Tj Proteins W Xie Et Almentioning

confidence: 70%

Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1 in LPS-induced mice

Xie

Wang

et al. 2013

Laboratory Investigation

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“…Angiotensin II has been shown to increase endothelial cell death, an effect that is reversed by increased haem oxygenase-1 gene expression [20,31]. Inhibition of haem oxygenase activity has been shown to exacerbate both the inflammatory response in the arterial wall and to enhance endothelial cell death and the expression of adhesion molecules in animal models of atherosclerosis [32].…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that human microvascular endothelial cells, when exposed to high glucose concentrations, manifest an increase in apoptosis [20]. We therefore hypothesised that hyperglycaemia-mediated oxidative stress results in endothelial cell injury and that this may be reflected by a concurrent increase in CECs.…”

Section: Introductionmentioning

confidence: 97%

Circulating endothelial cells are elevated in patients with type 2 diabetes mellitus independently of HbA1c

et al. 2005

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Aims/hypothesis: Patients with diabetes mellitus are well known to be at high risk for vascular disease. Circulating endothelial cells (CECs) have been reported to be an ex vivo indicator of vascular injury. We investigated the presence of CECs in the peripheral blood of 25 patients with diabetes mellitus and in nine nondiabetic control donors. Methods: Endothelial cells were isolated from peripheral blood with anti-CD-146-coated immunomagnetic Dynabeads, and were stained with acridine orange dye and counted by fluorescence microscopy. The cells were also stained for von Willebrand factor and Ulex europaeus lectin 1. Results: Patients with diabetes mellitus had an elevated number of CECs (mean 69±30 cells/ml, range 35-126) compared with healthy controls (mean 10±5 cells/ml, range 3-18) (p<0.001). The increase in CECs did not correlate with the levels of HbA 1 c. Circulating endothelial cell numbers were elevated regardless of glucose levels, suggesting that, even with control of glucose levels, there is increased endothelial cell sloughing. Conclusions: Our study suggests that the higher number of CECs in patients with type 2 diabetes may reflect ongoing vascular injury that is not directly dependent on glucose control.

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“…Plasma creatinine levels were measured using a commercial kit (Aldrich/Sigma), according to the manufacturer's recommendation. In renal tissue, superoxide measurements were performed using a cytochrome C assay that has been described previously (31).…”

Section: Animal Treatmentmentioning

confidence: 99%

“…Western Blot Analysis of HO-1 and HO-2. Homogenates were used as a source for the measurement of HO-1 and HO-2 proteins as described previously (31). Tissues were lysed in a buffer (lysis buffer B) that consisted of 0.5% Nonidet P-40, 0.5% deoxycholate, and 10 mM EDTA in Tris-buffered saline (20 mM Tris and 150 mM NaCl [pH 7.4]) that contained 10 g/ml each of leupeptin, antipain, and pepstatin and 1 mM PMSF.…”

mentioning

confidence: 99%

Heme Oxygenase-2 Deficiency Contributes to Diabetes-Mediated Increase in Superoxide Anion and Renal Dysfunction

Goodman¹,

Chander²,

Rezzani³

et al. 2006

Journal of the American Society of Nephrology

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Heme oxygenase-1 (HO-1) and -2 play an important role in cytoprotection and are physiologic regulators of heme-dependent protein synthesis in renal tissues. The impact of HO-2 deletion comparing hyperglycemic HO-2 (؉/؉) mice and HO-2 knockout (؊/؊) mice was examined. Hyperglycemia was induced by streptozotocin (STZ) injection, and its effect on renal HO-1/HO-2 protein, HO activity, and creatinine levels were assessed. The effect of HO induction using systemic administration of the HO inducers heme or cobalt protoporphyrin and the effect of HO inhibition using systemic administration of the HO inhibitor tin mesoporphyrin also were assessed in STZ-treated mice. In STZ-treated HO-2 (؊/؊) mice, there was marked renal functional impairment as reflected by an increase in plasma creatinine, associated with acute tubular damage and microvascular pathology as compared with HO-2 (؉/؉). In these animals, HO activity was decreased with a concomitant increase in superoxide anion. Upregulation of HO-1 in HO-2 (؊/؊) mice by weekly administration of cobalt protoporphyrin prevented the increase in plasma creatinine levels and tubulointerstitial and microvascular pathology. Inhibition of HO activity by administration of tin mesoporphyrin accentuated superoxide production and increased creatinine levels in hyperglycemic HO-2 (؊/؊) mice. In conclusion, HO-2 deficiency enhanced STZ-induced renal dysfunction and morphologic injury and HO-1 upregulation in HO-2 (؊/؊) mouse rescue and prevented the morphologic damage. These observations indicate that HO activity is essential in preserving renal function and morphology in STZ-induced diabetic mice probably via mitigation of concomitant oxidative stress.

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Heme Oxygenase-1 Attenuates Glucose-Mediated Cell Growth Arrest and Apoptosis in Human Microvessel Endothelial Cells

Cited by 140 publications

References 54 publications

Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1 in LPS-induced mice

Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1 in LPS-induced mice

Circulating endothelial cells are elevated in patients with type 2 diabetes mellitus independently of HbA1c

Heme Oxygenase-2 Deficiency Contributes to Diabetes-Mediated Increase in Superoxide Anion and Renal Dysfunction

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