Effect of Hypoxia on Endothelial Nitric Oxide Synthase, NO Production, Intracellular Survival Signaling (p-ERK1/2 and p-AKT) and Apoptosis in Human Term Trophoblast

• Published in: American journal of reproductive immunology (1989) Vol. 65; no. 4; pp. 407 - 414
• Main Authors: Park, Mi-Hye, Galan, Henry L., Arroyo, Juan A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2011
• Subjects: Apoptosis; Blotting, Western; Cell Hypoxia; Cells, Cultured; Endothelial Cells - cytology; Endothelial Cells - metabolism; eNOS; Female; Gene Expression; Humans; Hypoxia; In Situ Nick-End Labeling; Intracellular signalling; Media (culture); Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Oxygen; Parks; Phosphorylation; Pregnancy; Proto-Oncogene Proteins c-akt - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Survival; trophoblast; Trophoblasts; Trophoblasts - physiology; Western blotting
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/j.1600-0897.2010.00886.x

Citation Park M‐H, Galan HL, Arroyo JA. Effect of hypoxia on endothelial nitric oxide synthase, NO production, intracellular survival signaling (p‐ERK1/2 and p‐AKT) and apoptosis in human term trophoblast. Am J Reprod Immunol 2011; 65: 407–414 Problem  Hypoxia is commonly associated with complicated pregnancies such as intrauterine growth restriction. We evaluated the effects of hypoxia on phospho (p)‐eNOS, p‐ERK, p‐AKT and apoptosis in human trophoblast. Method of study  Isolated trophoblast were cultured in 21% oxygen or 2% oxygen for 24, 48 and 72 hr. p‐eNOS, p‐ERK and p‐AKT protein were assessed by Western blot and apoptosis by TUNEL assay. NOx was determined in the culture media. Results  Compared to controls, hypoxia‐exposed CT showed the following: (1) decreased eNOS at 48 and 72 hr, (2) increased p‐eNOS at 48 hr, (3) no differences in total NOx production, (4) increased p‐ERK at 24, 48 and 72 hr, (5) increased p‐AKT at 24 hr (P < 0.05) and (6) increased apoptosis at 48 hr. Conclusion  Hypoxia increases activation of p‐ERK and induces apoptosis of cultured trophoblast. Hypoxia decreases overall total eNOS but increases p‐eNOS, which may allow for NO production to be maintained in trophoblast cells.