title: SOD1 overexpression in vivo blocks hyperglycemia-induced specific PKC isoforms: substrate activation and consequent lipid peroxidation in diabetic embryopathy.
abstract: 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.
  
  
  METHODS
  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-) PKCα/βII and p-PKCδ, 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-PKCα/βII, p-PKCδ, 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.
  
  
  CONCLUSIONS
  Mitigating oxidative stress by SOD1 overexpression blocks maternal hyperglycemia-induced activation of specific PKC isoforms and downstream cascades.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Xuezheng
authors.initials: X
authors.lastname: Li
authors.forename: Hongbo
authors.initials: H
authors.lastname: Weng
authors.forename: E Albert
authors.initials: EA
authors.lastname: Reece
authors.forename: Peixin
authors.initials: P
authors.lastname: Yang
mesh_terms: D000447:Aldehydes / Q000097:blood; D000818:Animals; D048909:Diabetes Complications / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005260:Female; D005315:Fetal Diseases / Q000378:metabolism*; D006943:Hyperglycemia / Q000201:enzymology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009479:Neuropeptides / Q000378:metabolism; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D000072105:Superoxide Dismutase-1
chemical_list: D000447:Aldehydes; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D009479:Neuropeptides; C090294:RACK1 protein, mouse; D000075370:Receptors for Activated C Kinase; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D008315:Malondialdehyde; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; C027576:4-hydroxy-2-nonenal