Molecular and Cellular Biochemistry

, Volume 376, Issue 1–2, pp 121–135 | Cite as

Malondialdehyde and 4-hydroxynonenal adducts are not formed on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) in diabetes

  • Caronda J. Moore
  • Chun Hong Shao
  • Ryoji Nagai
  • Shelby Kutty
  • Jaipaul Singh
  • Keshore R. Bidasee
Article

Abstract

Recently, we reported an elevated level of glucose-generated carbonyl adducts on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) in hearts of streptozotocin(STZ)-induced diabetic rats. We also showed these adduct impaired RyR2 and SERCA2 activities, and altered evoked Ca2+ transients. What is less clear is if lipid-derived malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) also chemically react with and impair RyR2 and SERCA2 activities in diabetes? This study used western blot assays with adduct-specific antibodies and confocal microscopy to assess levels of MDA, 4-HNE, Nε-carboxy(methyl)lysine (CML), pentosidine, and pyrraline adducts on RyR2 and SERCA2 and evoked intracellular transient Ca2+ kinetics in myocytes from control, diabetic, and treated-diabetic rats. MDA and 4-HNE adducts were not detected on RyR2 and SERCA2 from either control or 8 weeks diabetic rats with altered evoked Ca2+ transients. However, CML, pentosidine, and pyrraline adducts were elevated three- to five-fold (p < 0.05). Treating diabetic rats with pyridoxamine (a scavenger of reactive carbonyl species, RCS) or aminoguanidine (a mixed reactive oxygen species-RCS scavenger) reduced CML, pentosidine, and pyrraline adducts on RyR2 and SERCA2 and blunted SR Ca2+ cycling changes. Treating diabetic rats with the superoxide dismutase mimetic tempol had no impact on MDA and 4-HNE adducts on RyR2 and SERCA2, and on SR Ca2+ cycling. From these data we conclude that lipid-derived MDA and 4-HNE adducts are not formed on RyR2 and SERCA2 in this model of diabetes, and are therefore unlikely to be directly contributing to the SR Ca2+ dysregulation.

Keywords

Diabetes mellitus Rats Malondialdehyde 4-Hydroxynonenal Post-translational modifications Type 2 ryanodine receptor Sarco(endo)plasmic reticulum Ca2+-ATPase 

Notes

Acknowledgments

The authors thank Janice A. Taylor and James R. Talaska of the Confocal Laser Scanning Microscope Core Facility at the University of Nebraska Medical Center for providing assistance with confocal microscopy. This work was supported in part by grants from the Edna Ittner Research Foundation, American Diabetes Association [1-06-RA-11] and the National Institutes of Health [HL085061].

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Caronda J. Moore
    • 1
  • Chun Hong Shao
    • 1
  • Ryoji Nagai
    • 2
  • Shelby Kutty
    • 3
  • Jaipaul Singh
    • 4
  • Keshore R. Bidasee
    • 1
    • 5
    • 6
  1. 1.Department of Pharmacology and Experimental Neuroscience, 985800 Nebraska Medical CenterDurham Research CenterOmahaUSA
  2. 2.Laboratory of Food and Regulation Biology, Department of Biosciences, School of AgricultureTokai UniversityTokyoJapan
  3. 3.Joint Division of Pediatric CardiologyUniversity of Nebraska/Creighton University and Children’s Hospital and Medical CenterOmahaUSA
  4. 4.School of Forensic and Investigative Sciences and School of Pharmacy and Biomedical SciencesUniversity of Central LancashirePrestonUK
  5. 5.Environmental, Agricultural and Occupational HealthUniversity of Nebraska Medical CenterOmahaUSA
  6. 6.N146 Beadle CenterNebraska Center for Redox BiologyLincolnUSA

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