Deficit of CD38/cyclic ADP-ribose is differentially compensated in hearts by gender.
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.
Takahashi
Jun
J
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Kagaya
Yutaka
Y
Kato
Ichiro
I
Ohta
Jun
J
Isoyama
Shogen
S
Miura
Masahito
M
Sugai
Yoshinao
Y
Hirose
Masanori
M
Wakayama
Yuji
Y
Ninomiya
Mototsugu
M
Watanabe
Jun
J
Takasawa
Shin
S
Okamoto
Hiroshi
H
Shirato
Kunio
K
D036541:ADP-ribosyl Cyclase / Q000172:deficiency*; D051997:ADP-ribosyl Cyclase 1; D000222:Adaptation, Physiological; D000818:Animals; D015703:Antigens, CD; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006332:Cardiomegaly / Q000503:physiopathology*; D036563:Cyclic ADP-Ribose / Q000172:deficiency*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006706:Homeostasis; D007527:Isoenzymes / Q000172:deficiency; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000503:physiopathology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012737:Sex Factors; D013314:Stress, Mechanical; D013696:Temperature; D000099211:Phospholamban
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D002118:Calcium; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D036563:Cyclic ADP-Ribose; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C498155:Cd38 protein, mouse; C506947:Atp2a2 protein, mouse