Deficit of CD38/cyclic ADP-ribose is differentially compensated in hearts by gender

Biochem Biophys Res Commun. 2003 Dec 12;312(2):434-40. doi: 10.1016/j.bbrc.2003.10.143.

Abstract

To elucidate whether myocardial CD38/cyclic ADP-ribose (cADPR) signaling plays a physiological role, we investigated the heart of CD38 knockout mice (CD38KO). In CD38KO, the myocardial cADPR content was reduced by 85% compared with wild-type mice (WT). Cardiac hypertrophy developed only in males. At 36 degrees C, none of the parameters for Ca(2+) transients and forces of the papillary muscles differed between WT and CD38KO. In contrast, at 27 degrees C, at which cADPR does not work, the peak [Ca(2+)](i) was increased and the decline in [Ca(2+)](i) was accelerated in CD38KO compared with WT. In CD38KO, the protein expression of SR Ca(2+) ATPase type2 (SERCA2) and the SERCA2-to-phospholamban ratio were increased compared with WT. The ryanodine receptor protein was increased only in female CD38KO compared with WT. These data suggest that the CD38/cADPR signaling plays an important role in intracellular Ca(2+) homeostasis in cardiac myocytes in vivo. Its deficiency was compensated differentially according to gender.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / deficiency*
  • ADP-ribosyl Cyclase 1
  • Adaptation, Physiological
  • Animals
  • Antigens, CD
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Signaling*
  • Calcium-Binding Proteins / metabolism
  • Calcium-Transporting ATPases / metabolism
  • Cardiomegaly / physiopathology*
  • Cyclic ADP-Ribose / deficiency*
  • Female
  • Heart / physiopathology*
  • Homeostasis
  • Isoenzymes / deficiency
  • Male
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Muscle Proteins / metabolism
  • Myocardial Contraction*
  • Myocardium / metabolism
  • Papillary Muscles / physiopathology
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sarcoplasmic Reticulum / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Sex Factors
  • Stress, Mechanical
  • Temperature

Substances

  • Antigens, CD
  • Calcium Channels
  • Calcium-Binding Proteins
  • Isoenzymes
  • Membrane Glycoproteins
  • Muscle Proteins
  • Ryanodine Receptor Calcium Release Channel
  • phospholamban
  • Cyclic ADP-Ribose
  • ADP-ribosyl Cyclase
  • Cd38 protein, mouse
  • ADP-ribosyl Cyclase 1
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Atp2a2 protein, mouse
  • Calcium-Transporting ATPases
  • Calcium