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Hydrogen peroxide‐induced redox homeostasis regulation in endothelial cells
Author(s) -
Patel Hemang,
Chen Juan,
Kavdia Mahendra
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.635.7
Subject(s) - homeostasis , chemistry , redox , oxidative stress , hydrogen peroxide , reactive oxygen species , microbiology and biotechnology , oxidative phosphorylation , superoxide , biochemistry , biology , enzyme , organic chemistry
Human vasculature is shown to regulate hydrogen peroxide (H 2 O 2 ) at various levels in normal as well as pathophysiological conditions. Recent research studies have put forward the involvement of H 2 O 2 in regulating cytotoxic and vasoactive response to vasculature. However, being part of redox system, the effect of H 2 O 2 on regulation of vascular and in particular endothelial redox system is not clearly understood. Thus, we investigated H 2 O 2 –induced regulation in redox system during transient and consistent exposure to endothelial cells. Using systems biology approach, we studied the superoxide (O₂‾) production, mitochondrial membrane polarization and gene expression of several redox system enzymes in HUVEC following both transient and consistent H 2 O 2 exposure for 72 hours. Our results, showed a significant down‐regulation in ASK1, CAT, TXNRD1 under continuous H 2 O 2 exposure. But in transient H 2 O 2 exposure followed by remodeling period showed significant up‐regulation in GPX1 and TXNRD1 whereas genes expression of ASK1, SOD1 and PRDX1 returned to homeostasis. In both treatment conditions, exposure to H₂O₂ significantly increased O₂‾ production, which remained significantly higher up to 48 hours and decreased back to control level. Similar trend was also observed in mitochondrial membrane polarization which transitioned from hyperpolarized to normal state over the period of 72 hours in both H₂O₂ treatment conditions. Results from our study indicate that HUVEC actively regulated functional and gene expression changes to reach similar extent of redox homeostasis under both H₂O₂ treatments. These results further the understanding on how endothelial cells endure varying levels of H₂O₂ in pathological conditions.