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

Jun Takahashi1, Yutaka Kagaya, Ichiro Kato

  • 1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

Biochemical and Biophysical Research Communications
|November 26, 2003
PubMed

Insights

CD38/cyclic ADP-ribose (cADPR) signaling is vital for heart calcium (Ca2+) balance. Its absence in mice caused gender-specific cardiac issues, highlighting its physiological role.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Physiology

Background:

  • CD38/cyclic ADP-ribose (cADPR) signaling's role in cardiac function is not fully understood.
  • Investigating this pathway is crucial for understanding intracellular calcium (Ca2+) homeostasis in the heart.

Purpose of the Study:

  • To determine the physiological role of myocardial CD38/cyclic ADP-ribose (cADPR) signaling in vivo.
  • To investigate the impact of CD38 deficiency on cardiac function and calcium handling.

Main Methods:

  • Utilized CD38 knockout mice (CD38KO) and wild-type (WT) littermates.
  • Measured myocardial cADPR content, cardiac hypertrophy, and papillary muscle contractility at different temperatures.
  • Assessed protein expression of key calcium-handling proteins, including SERCA2 and ryanodine receptors.

Main Results:

  • CD38KO mice exhibited an 85% reduction in myocardial cADPR content.
  • Cardiac hypertrophy was observed exclusively in male CD38KO mice.
  • At a non-permissive temperature (27°C), CD38KO showed altered Ca2+ transients and increased SERCA2 expression.
  • Gender-specific alterations in ryanodine receptor expression were noted in female CD38KO mice.

Conclusions:

  • CD38/cADPR signaling is essential for maintaining intracellular Ca2+ homeostasis in cardiac myocytes.
  • The absence of CD38 leads to compensatory mechanisms that differ between genders.
  • This study elucidates a significant physiological role for CD38/cADPR in cardiac health.

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