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Faculty of Science - Mahidol University

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<strong>Mahidol</strong> <strong>University</strong> Annual Research Abstracts, Vol. 33 333<br />

SIGNIFICANT EFFECTS OF ESTROGEN ON<br />

CARDIAC MYOFILAMENT ACTIVATION<br />

UNDER DIABETIC COMPLICATION (NO. 884)<br />

Ariyaporn Thawornkaiwong and Jonggonnee Wattanapermpool<br />

Department <strong>of</strong> Physiology, <strong>Faculty</strong> <strong>of</strong> <strong>Science</strong>, <strong>Mahidol</strong><br />

<strong>University</strong>. E-mail: tejwt@mahidol.ac.th<br />

Key words: estrogen, insulin, diabetes<br />

Deficiency <strong>of</strong> either estrogen (E 2 ) or insulin (Ins) suppresses<br />

maximum my<strong>of</strong>ibrillar ATPase activity to the same magnitude but<br />

only in ovariectomized (Ovx) hearts demonstrating my<strong>of</strong>ilament Ca 2+<br />

hypersensitivity. Surprisingly, no additive suppression in maximum<br />

my<strong>of</strong>ibrillar ATPase activity was observed in diabetic-Ovx (Diab-<br />

Ovx) hearts in which the Ca 2+ hypersensitivity was still present. We<br />

therefore hypothesized that the two hormones play a similar<br />

regulatory mechanism in maximum my<strong>of</strong>ibrillar ATPase activity but<br />

E 2 plays a dominant effect on myfilament Ca 2+ sensitivity. To<br />

investigate the potential regulatory pathway <strong>of</strong> the hormones on<br />

my<strong>of</strong>ilament activation, relations <strong>of</strong> %?-myosin heavy chain (?-<br />

MHC) and maximum ATPase activity were then examined. Despite<br />

the same ratio <strong>of</strong> ATPase to % ?-MHC detected in Ovx and control<br />

groups, the ratio in Diab group was significantly increased. These<br />

results indicate an adaptive response <strong>of</strong> crossbridge interaction in<br />

Ins deficient heart which may be resulted from the presentation <strong>of</strong><br />

E 2 . The same suppression <strong>of</strong> this ratio in Diab-Ovx hearts indicates<br />

beneficial effects <strong>of</strong> E 2 on cardiac adaptation in Diab rats. Concerning<br />

the proposed dominant role <strong>of</strong> E 2 in my<strong>of</strong>ilament Ca 2+<br />

hypersensitivity, the mobilization <strong>of</strong> intracellular Ca 2+ by<br />

sarcoplasmic reticulum (SR) was then focused. The SR Ca 2+ uptake<br />

activity and the expression <strong>of</strong> SR Ca 2+ ATPase (SERCA) were<br />

examined. Surprisingly, deficiency <strong>of</strong> both Ins and E 2 or <strong>of</strong> individual<br />

hormone caused reductions in both activity and expression <strong>of</strong><br />

SERCA to the same degree. Thus, the induction in my<strong>of</strong>ilament<br />

Ca 2+ hypersensitivity in E 2 deficient hearts may not be due to changes<br />

in intracellular Ca 2+ . Alterations in the my<strong>of</strong>ilament apparatus could<br />

serve as a potential target for the hormonal regulation. Results from<br />

the present study clearly indicate an essential role <strong>of</strong> E 2 in cardiac<br />

my<strong>of</strong>ilament activation especially under diabetic complication.<br />

(Supported by the Medical Scholar Program (MSP).<br />

CARDIO-PROTECTIVE EFFECTS OF EXERCISE<br />

TRAINING ON CHANGES IN SR Ca 2+ UPTAKE<br />

ACTIVITY IN OVARIECTOMIZED RATS (NO. 885)<br />

Jitanun Laosiripisan and Jonggonnee Wattanapermpool<br />

Department <strong>of</strong> Physiology, <strong>Faculty</strong> <strong>of</strong> <strong>Science</strong>, <strong>Mahidol</strong><br />

<strong>University</strong>. E-mail: tejwt@mahidol.ac.th<br />

Key words : estrogen, exercise training, SR Ca 2+ uptake, SR Ca 2+<br />

ATPase activity<br />

The use <strong>of</strong> hormone replacement therapy in postmenopausal<br />

women has been recently shown to induce many unfavorable effects,<br />

including cardiovascular defects, which then urges the studies <strong>of</strong><br />

other preventive or therapeutic alternatives. In the present study,<br />

preventive effects <strong>of</strong> exercise training on changes in cardiac SR Ca 2+<br />

uptake activity in 10-wk ovariectomized (OVX) rats were tested. A<br />

9-wk running program on a motor-driven treadmill was introduced<br />

to the exercise groups one week after surgery. The SR Ca 2+ uptake<br />

and SR Ca 2+ -ATPase (SERCA2a) activities were measured using<br />

left ventricular homogenate and SR vesicles, respectively.<br />

Significant suppressions in both Ca 2+ uptake and SERCA2a activities<br />

but increases in Ca 2+ uptake sensitivity were demonstrated in OVX<br />

hearts. Immunoblot analysis shows the downregulation <strong>of</strong> SERCA2a<br />

protein in OVX hearts with no change in the expression level <strong>of</strong> its<br />

regulatory protein called phospholamban (PLB). It is the<br />

phosphorylation <strong>of</strong> PLB either at Ser-16 or Thr-17 residues that will<br />

release its inhibitory action on SERCA2a. The amounts <strong>of</strong> these<br />

phosphorylated forms <strong>of</strong> PLB were then analysed using Western blot<br />

probing with individual phosphorylated-PLB antibody. There was<br />

a significant reduction in phospho-Thr-17-PLB in OVX hearts, in<br />

which exercise training could also prevent the change. These results<br />

indicate the cardio-protective effects <strong>of</strong> exercise training on changes<br />

in cardiac SR Ca 2+ uptake activities in OVX rats via restoration <strong>of</strong><br />

both the amount and activity <strong>of</strong> SERCA2a protein.<br />

(Supported by The Thailand Research Fund, <strong>Faculty</strong> <strong>of</strong> <strong>Science</strong>, and<br />

<strong>Mahidol</strong> <strong>University</strong>)<br />

SIGNIFICANCE OF ESTROGEN ON CARDIAC<br />

CONTRACTILE ACTIVITY & THE BENEFIT OF<br />

PHYTOESTROGENS (NO. 886)<br />

Jonggonnee Wattanapermpool<br />

Department <strong>of</strong> Physiology, <strong>Faculty</strong> <strong>of</strong> <strong>Science</strong>, <strong>Mahidol</strong><br />

<strong>University</strong>. E-mail: tejwt@mahidol.ac.th<br />

Key words: estrogen, cardiac contractile activity, exercise training<br />

An important question related to the well recognizable sex<br />

difference in the incidence <strong>of</strong> cardiovascular diseases is the<br />

significance <strong>of</strong> sex hormones on the cardiovascular system especially<br />

on the cardiac contractile function. Although the receptors are<br />

present in the cardiac myocardium, the regulatory role <strong>of</strong> estrogen<br />

in the cardiac contractile activity is still unclear. A series <strong>of</strong><br />

experimental studies using ovariectomized rats as a model <strong>of</strong> estrogen<br />

deficiency have demonstrated a significant role <strong>of</strong> estrogen in<br />

regulating the cardiac contractile activity. Changes in the<br />

intracellular Ca 2+ in signaling the contraction/relaxation cycle were<br />

largely contributed by alterations in Ca 2+ handling process <strong>of</strong> the<br />

cardiac myocytes. Besides hormone replacement therapy, exercise<br />

training and phytoestrogens could be other alternative modes for<br />

the cardio-protection.<br />

(Supported by The Thailand Research Fund, <strong>Faculty</strong> <strong>of</strong> <strong>Science</strong>, and<br />

<strong>Mahidol</strong> <strong>University</strong>)<br />

SECRETION OF CARNITINE IN THE DISTAL<br />

CAPUT EPIDIDYMIDIS OF RATS PERFUSED<br />

IN VITRO (NO. 887)<br />

Chumpol Pholpramool and Kanokporn Poungpong<br />

Department <strong>of</strong> Physiology, <strong>Faculty</strong> <strong>of</strong> <strong>Science</strong>, <strong>Mahidol</strong><br />

<strong>University</strong>. E-mail: sccpp@mahidol.ac.th<br />

Key words : carnitine transporter, rat epididymis, carnitine<br />

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