Journal
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
Volume 205, Issue 1, Pages -Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.ajog.2011.02.071
Keywords
diabetic embryopathy; lipid peroxidation; myristoylated alanine-rich protein kinase C substrate; protein kinase C isoforms; superoxide dismutase 1 transgenic mice
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Funding
- National Institutes of Health [R01DK083243, R01 DK083770]
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OBJECTIVE: Oxidative stress plays a causative role in diabetic embryopathy. We tested whether mitigating oxidative stress, using superoxide dismutase 1 (SOD1) transgenic (Tg) mice, would block hyperglycemia-induced specific protein kinase C (PKC) isoform activation and its downstream cascade. STUDY DESIGN: Day 8.5 embryos from nondiabetic wild-type control (NC), diabetic mellitus wild-type (DM), and diabetic SOD1-Tg mice (DM-SOD1-Tg) were used for detection of phosphorylated (p-) PKC alpha/beta II and p-PKC delta, and levels of 2 prominent PKC substrates, phosphorylated myristoylated alanine-rich protein kinase C substrate (MARCKS) and receptor for activated C kinase 1 (RACK1), and lipid peroxidation markers, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). RESULTS: Levels of p-PKC alpha/beta II, p-PKC delta, p-MARCKS, 4-HNE, and MDA were significantly elevated in the DM group compared with those in the NC group and the DM-SOD1-Tg group. The NC and DM-SOD1-Tg groups had comparable levels of these protein and lipid peroxidation markers. RACK1 levels did not differ among the 3 groups. CONCLUSION: Mitigating oxidative stress by SOD1 overexpression blocks maternal hyperglycemia-induced activation of specific PKC isoforms and downstream cascades.
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