Decreases in manganese superoxide dismutase expression and activity contribute to oxidative stress in persistent pulmonary hypertension of the newborn

Afolayan, Adeleye J.; Eis, Annie; Teng, Ru-Jeng; Bakhutashvili, Ivane; Kaul, Sushma; Davis, Jonathan M.; Konduri, Girija G.

doi:10.1152/ajplung.00098.2012

Cited by 61 publications

(80 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the MnSOD protein levels only increased by one-third, MnSOD-specific activity in IPH PAECs increased significantly, by approximately 56%, from 2.84 (6 0.12) to 4.43 (6 0.15) U/mg protein after NgBR overexpression (n = 5, P , 0.05). Our previous observation that impaired MnSOD transport into mitochondria contributes significantly to the decreased MnSOD activity in IPH PAECs may explain the discrepancy between MnSOD levels and MnSOD activity that we observed in this study (19).…”

Section: Ngbr Modulates Enos Coupling and The Levels Of Mnsod And Gtpcontrasting

confidence: 86%

“…MnSOD-specific activity was measured using a colorimetric assay (Cayman Chemical, Ann Arbor, MI) and was normalized to the protein content (19). Absorbance was read at 450 nm.…”

Section: Mnsod Activity Assaymentioning

confidence: 99%

“…IPH PAECs also show impaired in vitro and ex vivo angiogenesis, which may contribute to the histological and physiological changes in PPHN (18). We also reported that expression and activity of manganese superoxide dismutase (MnSOD) are decreased in IPH PAECs, which further increased ROS formation (19). Nogo-A is known to antagonize ROS generation and protects premature cortical neurons (20).…”

mentioning

confidence: 94%

See 2 more Smart Citations

Nogo-B Receptor Modulates Angiogenesis Response of Pulmonary Artery Endothelial Cells Through eNOS Coupling

Teng¹,

Rana²,

Afolayan³

et al. 2014

Am J Respir Cell Mol Biol

Self Cite

View full text Add to dashboard Cite

Nogo-B, a reticulon-4 isoform, modulates the motility and adhesion of vascular endothelial cells after binding to its receptor, Nogo-B receptor (NgBR). Nogo-B/NgBR pathway contributes to vascular remodeling and angiogenesis, but the role of this pathway in the angiogenesis of developing lungs remains unknown. We previously reported that angiogenesis function of pulmonary artery endothelial cells (PAECs) is impaired by increased reactive oxygen species formation in a fetal lamb model of intrauterine pulmonary hypertension (IPH). Here, we report that Nogo-B/NgBR pathway is altered in IPH, and that decreased NgBR expression contributes to impaired angiogenesis in IPH. We observed a decrease in NgBR levels in lysates of whole lung or PAECs from fetal lambs with IPH compared with controls. Overexpression of NgBR in IPH PAECs rescued the in vitro angiogenesis defects and increased the phosphorylation of both Akt and endothelial nitric oxide synthase at serine 1179 as well as the levels of both manganese superoxide dismutase and GTP cyclohydrolase-1. Consistent with the phenotype of IPH PAECs, knockdown of NgBR in control PAECs decreased the levels of nitric oxide, increased the levels of reactive oxygen species, and impaired in vitro angiogenesis. Our data demonstrate that NgBR mediates PAEC angiogenesis response through the modulation of Akt/endothelial nitric oxide synthase functions, and its decreased expression is mechanistically linked to IPH-related angiogenesis defects in the developing lungs.

show abstract

Section: Ngbr Modulates Enos Coupling and The Levels Of Mnsod And Gtpcontrasting

confidence: 86%

“…MnSOD-specific activity was measured using a colorimetric assay (Cayman Chemical, Ann Arbor, MI) and was normalized to the protein content (19). Absorbance was read at 450 nm.…”

Section: Mnsod Activity Assaymentioning

confidence: 99%

mentioning

confidence: 94%

See 1 more Smart Citation

Nogo-B Receptor Modulates Angiogenesis Response of Pulmonary Artery Endothelial Cells Through eNOS Coupling

Teng¹,

Rana²,

Afolayan³

et al. 2014

Am J Respir Cell Mol Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…PAECs were isolated from near-term lambs of either gender as described previously (33,42). The PAEC identity was confirmed by CD31 (550274, BD Biosciences) staining for each experiment.…”

Section: Methodsmentioning

confidence: 99%

Domain Mapping of Heat Shock Protein 70 Reveals That Glutamic Acid 446 and Arginine 447 Are Critical for Regulating Superoxide Dismutase 2 Function

Afolayan

Alexander

Holme

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Edited by Linda SpremulliStress-inducible heat shock protein 70 (hsp70) interacts with superoxide dismutase 2 (SOD2) in the cytosol after synthesis to transfer the enzyme to the mitochondria for subsequent activation. However, the structural basis for this interaction remains to be defined. To map the SOD2-binding site in hsp70, mutants of hsp70 were made and tested for their ability to bind SOD2. These studies showed that SOD2 binds in the amino acid 393-537 region of the chaperone. To map the hsp70-binding site in SOD2, we used a series of pulldown assays and showed that hsp70 binds to the amino-terminal domain of SOD2. To better define the binding site, we used a series of decoy peptides derived from the primary amino acid sequence in the SOD2-binding site in hsp70. This study shows that SOD2 specifically binds to hsp70 at 445 GERAMT 450 . Small peptides containing GERAMT inhibited the transfer of SOD2 to the mitochondria and decreased SOD2 activity in vitro and in vivo. To determine the amino acid residues in hsp70 that are critical for SOD2 interactions, we substituted each amino acid residue for alanine or more conservative residues, glutamine or asparagine, in the GERAMT-binding site. Substitutions of E446A/Q and R447A/Q inhibited the ability of the GERAMT peptide to bind SOD2 and preserved SOD2 function more than other substitutions. Together, these findings indicate that the GERAMT sequence is critical for hsp70-mediated regulation of SOD2 and that Glu 446 and Arg 447 cooperate with other amino acid residues in the GERAMT-binding site for proper chaperone-dependent regulation of SOD2 antioxidant function.

show abstract

“…In the same report we also observed an increased GTP cyclohydrolase-1 level and MnSOD level/activity. Judging from the decreased GTP cyclohydrolase-1 level [33] and MnSOD level/activity in IPH PAEC [34] impair angiogenesis in IPH we believe NgBR provides several levels of benefit to vascular development in the developing lungs.…”

Section: Function Of Ngbrmentioning

confidence: 91%

Nogo-B Receptor (NgBR): A New Receptor that Modulates Blood Vessel Formation

Teng

2014

Receptor Clin Invest

View full text Add to dashboard Cite

show abstract

Decreases in manganese superoxide dismutase expression and activity contribute to oxidative stress in persistent pulmonary hypertension of the newborn

Cited by 61 publications

References 46 publications

Nogo-B Receptor Modulates Angiogenesis Response of Pulmonary Artery Endothelial Cells Through eNOS Coupling

Nogo-B Receptor Modulates Angiogenesis Response of Pulmonary Artery Endothelial Cells Through eNOS Coupling

Domain Mapping of Heat Shock Protein 70 Reveals That Glutamic Acid 446 and Arginine 447 Are Critical for Regulating Superoxide Dismutase 2 Function

Nogo-B Receptor (NgBR): A New Receptor that Modulates Blood Vessel Formation

Contact Info

Product

Resources

About