Protein kinase C delta regulates anti-apoptotic alphaB-crystallin in the retina of type 2 diabetes

Neurobiol Dis. 2007 Dec;28(3):293-303. doi: 10.1016/j.nbd.2007.07.017. Epub 2007 Jul 26.

Abstract

We investigated the relationship between phosphorylation of alphaB-crystallin (alphaBC) and retinal apoptosis in type 2 diabetes. The retinas of male Otsuka Long-Evans Tokushima fatty (OLETF) rats at 24 and 35 weeks were used as an animal model for type 2 diabetes and sex- and age-matched Long-Evans Tokushima Otsuka (LETO) rats were used as controls. In the retinas of 35-week OLETF rats, the interaction between alphaBC and protein kinase C delta (PKC delta) among the PKC isozymes, alphaBC phosphorylation at Ser45 (S45p-alphaBC), TUNEL-positive apoptotic ganglion cells, several apoptotic signs, and co-localization of S45p-alphaBC and TUNEL significantly increased as compared with other groups while the alphaBC-Bax interaction greatly decreased. These changes were abolished by rottlerin treatment, a highly specific PKC delta inhibitor. These results suggest that PKC delta is involved in regulation of anti-apoptotic function of alphaBC in the retina of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology
  • Age Factors
  • Animals
  • Apoptosis / physiology
  • Benzopyrans / pharmacology
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Body Weight / physiology
  • Diabetes Mellitus, Type 2 / pathology*
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gene Expression Regulation
  • Immunoprecipitation / methods
  • In Situ Nick-End Labeling
  • Male
  • Protein Kinase C-delta / physiology*
  • Rats
  • Rats, Inbred OLETF
  • Rats, Long-Evans
  • Retina / drug effects
  • Retina / metabolism*
  • Retina / pathology
  • Time Factors
  • alpha-Crystallin B Chain / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Acetophenones
  • Benzopyrans
  • Blood Glucose
  • Enzyme Inhibitors
  • alpha-Crystallin B Chain
  • bcl-2-Associated X Protein
  • rottlerin
  • Protein Kinase C-delta