TNF-α-mediated cell death is attenuated by retrovirus delivery of human heme oxygenase-1 gene into human microvessel endothelial cells

2002 ◽  
Vol 34 (7) ◽  
pp. 2973-2978 ◽  
Author(s):  
T Kushida ◽  
G LiVolti ◽  
A.I Goodman ◽  
N.G Abraham
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Tnf Α ◽  
Microvessel Endothelial Cells

Resveratrol increases vascular oxidative stress resistance

2007 ◽  
Vol 292 (5) ◽  
pp. H2417-H2424 ◽  
Author(s):  
Zoltan Ungvari ◽  
Zsuzsanna Orosz ◽  
Aracelie Rivera ◽  
Nazar Labinskyy ◽  
Zhao Xiangmin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Glutathione Peroxidase ◽  
Heme Oxygenase ◽  
Stress Resistance ◽  
Heme Oxygenase 1 ◽  
Resveratrol Treatment ◽  
Vascular Oxidative Stress

Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. However, the mechanisms by which resveratrol exerts its vasculoprotective effects are not completely understood. Because oxidative stress and endothelial cell injury play a critical role in vascular aging and atherogenesis, we evaluated whether resveratrol inhibits oxidative stress-induced endothelial apoptosis. We found that oxidized LDL and TNF-α elicited significant increases in caspase-3/7 activity in endothelial cells and cultured rat aortas, which were prevented by resveratrol pretreatment (10−6–10−4 mol/l). The protective effect of resveratrol was attenuated by inhibition of glutathione peroxidase and heme oxygenase-1, suggesting a role for antioxidant systems in the antiapoptotic action of resveratrol. Indeed, resveratrol treatment protected cultured aortic segments and/or endothelial cells against increases in intracellular H2O2 levels and H2O2-mediated apoptotic cell death induced by oxidative stressors (exogenous H2O2, paraquat, and UV light). Resveratrol treatment also attenuated UV-induced DNA damage (comet assay). Resveratrol treatment upregulated the expression of glutathione peroxidase, catalase, and heme oxygenase-1 in cultured arteries, whereas it had no significant effect on the expression of SOD isoforms. Resveratrol also effectively scavenged H2O2 in vitro. Thus resveratrol seems to increase vascular oxidative stress resistance by scavenging H2O2 and preventing oxidative stress-induced endothelial cell death. We propose that the antioxidant and antiapoptotic effects of resveratrol, together with its previously described anti-inflammatory actions, are responsible, at least in part, for its cardioprotective effects.

scholarly journals Epigallocatechin gallate induces expression of heme oxygenase-1 in endothelial cells via p38 MAPK and Nrf-2 that suppresses proinflammatory actions of TNF-α

2012 ◽  
Vol 23 (9) ◽  
pp. 1134-1145 ◽  
Author(s):  
Philomena Pullikotil ◽  
Hui Chen ◽  
Ranganath Muniyappa ◽  
Cynthia C. Greenberg ◽  
Shutong Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Heme Oxygenase ◽  
Epigallocatechin Gallate ◽  
Heme Oxygenase 1 ◽  
Tnf Α

TNF-α and IL-1α induce heme oxygenase-1 via protein kinase C, Ca2+, and phospholipase A2 in endothelial cells

1999 ◽  
Vol 276 (5) ◽  
pp. H1493-H1501 ◽  
Author(s):  
Christi M. Terry ◽  
Jennifer A. Clikeman ◽  
John R. Hoidal ◽  
Karleen S. Callahan
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Heme Oxygenase ◽  
Calcium Ionophore ◽  
Heme Oxygenase 1 ◽  
Acetoxymethyl Ester ◽  
Cytokine Induction ◽  
Kinase C ◽  
Tnf Α

Heme oxygenase-1 (HO-1), an enzyme important in protection against oxidant stress, is induced in human vascular endothelial cells by the cytokines tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α). However, the signaling mediators that regulate the induction are not known. This study examined the involvement of protein kinase C (PKC), phospholipase A2(PLA2), calcium, and oxidants in cytokine induction of HO-1. Acute exposure to the PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated HO-1 mRNA. However, prolonged exposure, which downregulates most PKC isoforms, blocked induction of HO-1 mRNA by IL-1α and TNF-α. Additionally, the phosphatase inhibitors okadaic acid and calyculin enhanced cytokine induction of HO-1. Mepacrine, a PLA2 inhibitor, prevented HO-1 induction by cytokine, suggesting a role for arachidonate, the product of PLA2hydrolysis of phospholipids, in HO-1 expression. The intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM) blocked cytokine induction of HO-1. Paradoxically, the calcium ionophore A-23187 prevented HO-1 induction by cytokine but not by PMA. Finally, the oxidant scavenger N-acetylcysteine inhibited HO-1 induction by cytokines. These results demonstrate that TNF-α and IL-1α induction of HO-1 requires PKC-mediated phosphorylation and PLA2 activation as well as oxidant generation.

scholarly journals Heme oxygenase-1 is a potent inhibitor of placental ischemia-mediated endothelin-1 production in cultured human glomerular endothelial cells

2018 ◽  
Vol 314 (3) ◽  
pp. R427-R432 ◽  
Author(s):  
Bhavisha A. Bakrania ◽  
Frank T. Spradley ◽  
Simon C. Satchell ◽  
David E. Stec ◽  
John M. Rimoldi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Critical Role ◽  
Heme Oxygenase 1 ◽  
Endothelin 1 ◽  
Arterial Blood ◽  
Glomerular Endothelial Cells ◽  
Tnf Α ◽  
Human Glomerular Endothelial Cells ◽  
Placental Ischemia

Preeclampsia is a pregnancy-specific disorder of maternal hypertension and reduced renal hemodynamics linked to reduced endothelial function. Placental ischemia is thought to be the culprit of this disease, as it causes the release of factors like tumor necrosis factor (TNF)-α that induce vascular endothelin-1 (ET-1) production. Interestingly, placental ischemia-induced hypertension in rats [reduced uterine perfusion pressure (RUPP) model] is abolished by ETA receptor blockade, suggesting a critical role for ET-1. Although it has been found that systemic induction of heme oxygenase (HO)-1 is associated with reduced ET-1 production and attenuated hypertension, it is unclear whether HO-1 directly modulates the increased ET-1 response to placental factors. We tested the hypothesis that HO-1 or its metabolites inhibit ET-1 production in human glomerular endothelial cells induced by serum of RUPP rats or TNF-α. Serum (5%) from RUPP hypertensive (mean arterial blood pressure 119 ± 9 mmHg) vs. normotensive pregnant (NP, 101 ± 6 mmHg, P < 0.001) rats increased ET-1 production (RUPP 168.8 ± 18.1 pg/ml, NP 80.3 ± 22.7 pg/ml, P < 0.001, n = 12/group). HO-1 induction [25 µM cobalt photoporphyrin (CoPP)] abolished RUPP serum-induced ET-1 production (1.6 ± 0.8 pg/ml, P < 0.001), whereas bilirubin (10 µM) significantly attenuated ET-1 release (125.3 ± 5.2 pg/ml, P = 0.005). Furthermore, TNF-α-induced ET-1 production (TNF-α 31.0 ± 8.4 vs. untreated 7.5 ± 0.4 pg/ml, P < 0.001) was reduced by CoPP (1.5 ± 0.8 pg/ml, P < 0.001) and bilirubin (10.5 ± 4.3 pg/ml, P < 0.001). These results suggest that circulating factors released during placental ischemia target the maternal glomerular endothelium to increase ET-1, and that pharmacological induction of HO-1 or bilirubin could be a treatment strategy to block this prohypertensive pathway in preeclampsia.

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

2003 ◽  
Vol 93 (6) ◽  
pp. 507-514 ◽  
Author(s):  
Nader G. Abraham ◽  
Taketoshi Kushida ◽  
Jack McClung ◽  
Melvin Weiss ◽  
Shuo Quan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Growth ◽  
Heme Oxygenase ◽  
Growth Arrest ◽  
Heme Oxygenase 1 ◽  
Cell Growth Arrest ◽  
Microvessel Endothelial Cells

Effect of tumor necrosis factor-α and interleukin-1α on heme oxygenase-1 expression in human endothelial cells

1998 ◽  
Vol 274 (3) ◽  
pp. H883-H891 ◽  
Author(s):  
Christi M. Terry ◽  
Jennifer A. Clikeman ◽  
John R. Hoidal ◽  
Karleen S. Callahan
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Heme Oxygenase ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Heme Oxygenase 1 ◽  
Human Endothelial Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Heme iron exacerbates oxidant damage by catalyzing the production of free radicals. Heme oxygenase is the rate-limiting enzyme involved in heme catabolism. An inducible form of heme oxygenase, heme oxygenase-1 (HO-1), is upregulated in oxidant and inflammatory settings, and recent work suggests that HO-1 induction may serve a protective function against oxidant injury. The ability of the endogenous inflammatory mediators, interleukin (IL)-1α, tumor necrosis factor-α (TNF-α), and IL-6, to enhance HO-1 expression in cultured human endothelial cells was examined in this study. HO-1 mRNA and protein expression were upregulated by IL-1α and TNF-α exposure but not by IL-6. Induction of HO-1 mRNA by IL-1α and TNF-α occurred in a concentration- and time-dependent fashion, with maximal expression occurring by 4 h for both cytokines. Induction depended on protein synthesis and occurred at the transcriptional level. Inhibition of the AP-1 transcription factor with curcumin decreased the cytokine induction of HO-1 mRNA, suggesting the involvement of this transcription factor in cytokine signaling of HO-1. The results of this study indicate that the endogenous inflammatory cytokines IL-1α and TNF-α induce HO-1 in endothelial cells, providing further evidence that HO-1 may be an important cellular response to inflammatory stress.

scholarly journals Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survival

2009 ◽  
Vol 297 (4) ◽  
pp. C907-C915 ◽  
Author(s):  
Yong Wei ◽  
Xiao-ming Liu ◽  
Kelly J. Peyton ◽  
Hong Wang ◽  
Fruzsina K. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Mitochondrial Dysfunction ◽  
Heme Oxygenase ◽  
Hypochlorous Acid ◽  
Significant Rise ◽  
Dominant Negative Mutant ◽  
Heme Oxygenase 1

Hypochlorous acid (HOCl) is a unique oxidant generated by the enzyme myeloperoxidase that contributes to endothelial cell dysfunction and death in atherosclerosis. Since myeloperoxidase localizes with heme oxygenase-1 (HO-1) in and around endothelial cells of atherosclerotic lesions, the present study investigated whether there was an interaction between these two enzymes in vascular endothelium. Treatment of human endothelial cells with the myeloperoxidase product HOCl stimulated a concentration- and time-dependent increase in HO-1 protein that resulted in a significant rise in carbon monoxide (CO) production. The induction of HO-1 protein was preceded by a prominent increase in HO-1 mRNA and total and nuclear factor-erythroid 2-related factor 2 (Nrf2). In addition, HOCl induced a significant rise in HO-1 promoter activity that was blocked by mutating the antioxidant response element (ARE) in the promoter or by overexpressing a dominant-negative mutant of Nrf2. The HOCl-mediated induction of Nrf2 or HO-1 was blocked by the glutathione donor N-acetyl-l-cysteine but was unaffected by ascorbic or uric acid. Finally, treatment of endothelial cells with HOCl stimulated mitochondrial dysfunction, caspase-3 activation, and cell death that was potentiated by the HO inhibitor, tin protoporphyrin-IX, or by the knockdown of HO-1, and reversed by the exogenous administration of biliverdin, bilirubin, or CO. These results demonstrate that HOCl induces HO-1 gene transcription via the activation of the Nrf2/ARE pathway to counteract HOCl-mediated mitochondrial dysfunction and cell death. The ability of HOCl to activate HO-1 gene expression may represent a critical adaptive response to maintain endothelial cell viability at sites of vascular inflammation and atherosclerosis.

scholarly journals Characterization of Heme Oxygenase 1 (Heat Shock Protein 32) Induction by Atrial Natriuretic Peptide in Human Endothelial Cells

Endocrinology ◽  
2003 ◽  
Vol 144 (3) ◽  
pp. 802-812 ◽  
Author(s):  
Alexandra K. Kiemer ◽  
Nicole Bildner ◽  
Nina C. Weber ◽  
Angelika M. Vollmar
Keyword(s):  
Endothelial Cells ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Reporter Gene ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Reporter Gene Assays ◽  
Atrial Natriuretic

Background: Atrial natriuretic peptide (ANP) is a cardiovascular hormone possessing antiinflammatory and cytoprotective potential. The aim of this study was to characterize induction of heme oxygenase (HO)-1 by ANP in human umbilical vein endothelial cells (HUVEC). Methods: HUVEC were treated with ANP, 8-bromo-cyclic GMP (cGMP), or cANF in the presence or absence of various inhibitors. HO-1 was determined by Western blot and RT-PCR, c-jun N-terminal kinase (JNK) and ERK by the use of phospho-specific antibodies. Activator protein (AP)-1 activation was assessed by gelshift assay. Reporter gene assays were performed using native or mutated AP-1 binding sites of the HO-1 promoter. TNF-α-induced cell death was investigated by Hoechst staining, fluorescence-activated cell sorting analysis, caspase-3-measurement, and 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Results: ANP (10−9–10−6 mol/liter) induced the expression of HO-1 protein and mRNA. Induction was mediated via the guanylate-cyclase-coupled receptor because 8-Br-cGMP mimicked the effect of ANP, whereas the clearance receptor agonist cANF did not induce HO-1. Endogenously produced cGMP also induced HO-1 because phosphodiesterase inhibition markedly elevated HO-1. The lack of effect of the cGMP-dependent protein kinase inhibitor 8-(4-chlorophenylthio)guanosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-8-pCT-cGMPS) suggested no involvement for this cGMP effector pathway in the signal transduction. ANP lead to activation of the transcription factor AP-1, and subsequently of JNK, as well as of ERK. Cotreatment of the cells with U0126 or SP600125, as well as reporter gene assays revealed the involvement of AP-1/JNK activation in HO-1 induction. Abrogation of HO-1 induction by PD-98059 showed also a role for ERK. Treatment of HUVEC with ANP did not protect from TNF-α-induced apoptosis. Conclusion: This work characterizes the induction of HO-1 by ANP in HUVEC, which is shown to be mediated via JNK/AP-1 and ERK pathways. ANP-induced HO-1 does not confer protection against TNF-α-induced apoptosis.

Sign in / Sign up

Export Citation Format

Share Document