• BMB Reports
• /
• 제45권12호
• /
• pp.742-747
• /
• 2012

Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent ($H_2O_2$). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure.

• Applied Microscopy
• /
• 제20권2호
• /
• pp.127-159
• /
• 1990

This study was investigated to elucidate the effect of chlorambucil on the heart in aging rats. Male rat ranging in age from 3 to 36 months were used. Each age groups(3, 6, 12, 18, 24, 36 months) included control and chlorambucil treated rats. As a part of the study, the ultrastructural changes in the left ventricular myocardial cells were described by using the qualitative and morphometric techniques. The results are summarized as follows. Age associated ultrastructural changes included: an increase in vacuoles, protrusion of plasma membranes, lipid droplets, and lipofuscins in myocardium of control groups. These changes which begin to occur at 12 months and continue through 36 months. At the 36 months some instance of unusual formation of contraction band and separation of intercalated discs were encountered. Morever, these changes and contents with chlorambucil treatment were remarkably increased in comparison with control groups. Age-dependent changes of control group measured with morphometry were not observed in the volume densities of mitochondria and myofibrils. But there was increase in interstitium. On the other hand decrease in sarcoplasmic reticulum and T-tubule system. In chlorambucil treated groups, volume densities of mitochondria and interstitium were increased in comparison with those of the control groups. But sarcoplasmic reticulum and T-tubule system were remarkably decreased.

• 한국동물위생학회지
• /
• 제33권4호
• /
• pp.411-415
• /
• 2010

The present study was devised to determine the effects of body weight, organ weight, hematological values and biochemical parameters by vitamin E and selenium (Selevit) in the ovariectomized (OVX) rats. The animals were divided into 4 groups. Intact group (n=10) received no treatment and operation. Sham group (n=10) received only sham operation and no treatment. OVX group received operation and no treatment. OVX+Selevit received operation and Selevit. The body weights of the all group increased, and that of OVX+Selevit group was the lowest rates. There were significant differences (P<0.01, P<0.001) of body weights between OVX+Selevit group and all other groups. Also, organ weights such as heart, liver, spleen and kidney were measured. The heart and liver weight were significantly lower (P<0.01, P<0.001) in the OVX+Selevit group than in the Intact and Sham group. Also, the kidney weight was significantly lower (P<0.05, P<0.01) in the OVX+Selevit group than in the all other group. On the other hand, there was no significantly difference in the organ weight of spleen between the OVX+Selevit group and the other groups. The number of WBC was significantly higher (P<0.05) in the OVX+Selevit group than in the all other groups. The hematological values of RBC, MCV, MCH and MCHC were no significant differences in any groups. The biochemical parameters of serum total protein and alkaline phosphatase increased significantly in the OVX+Selevit group as compared to that in the OVX group. But, there were no significant differences in AST and ALT in any groups. We conclude that vitamin E and selenium were significantly decreased the body weights in the ovariectomized rats. Our findings suggest that vitamin E and selenium may influence the process of lipid packaging and absorption in the ovariectomized rats.

• 대한약리학회지
• /
• 제30권1호
• /
• pp.59-65
• /
• 1994

기아(starvation)기간중 흰쥐의 심근세포내에 심장의 수축 기능에 필요한 내인성 대사 기질인 지질의 축적이 증가된다는 사실이 알려져 있다. 본 연구에서는 lidocaine의 심근내 지방대사에 대한 영향을 기능적 측면에서 관찰하기 위하여, 굶긴 쥐 적출 심장의 수축성에 대한 lidocaine의 영향을 검토한바 다음과 같은 실험결과를 얻었다. 1. 굶긴 쥐 체중은 정상쥐에 비하여 현저히 감소되었으며, 기아시작 4일에서 약 30%의 체중감소를 나타했다. 그러나 정상쥐의 체중은 증가되었다. 2. 정상 쥐의 적출 심방은 기질제거 용액에서 30분에 약 40%의 현저한 수축력의 감소를 보였다. 그러나 2일간 굶긴 쥐의 적출 심장은 기질제거용액에서 30분에 약 13%의 수축력의 감소를 보여 정상 쥐에서의 수축력 저하보다 현저히 낮은 감소율을 나타냈다. 3. Lidocaine(0.1mM)에 의한 흰쥐 적출 심장의 수축력 감소는 정상쥐에 비해 굶긴 쥐 적출 심장의 수축력이 작게 감소되었다. 또한, lidocaine에 의한 굶긴 쥐 적출심장의 감소율은, 1일간 굴긴 쥐 보다 2일간 굴긴 쥐의 적출심장이 현저히 더 작게 감소되었다. 이상의 결과로 미루어 보아, 굶기는 동안 쥐 심근 내에 축적된 내인성 대사 기질인 지질이 lidocaine에 의해 해당과정이 억제된 심장의 수축과정에 energy원으로 쓰여지고 있을 가능성을 시사하고 있다.

• Journal of Chest Surgery
• /
• 제26권2호
• /
• pp.75-79
• /
• 1993

Myocardial protection against ischemic and reperfusion injuries is still in troublesome eventhough couples of the way of myocardial protection have been applied since 1970's. One of the possibility in myocardial protection is adding Fructose-l,6-diphosphate(FDP) in cardioplegic solution. It is assumed that FDP can promote ATP production under anaerobic condition as well as inhibiting the supressing effect of lactate on phosphofructokinase. We compared the myocardial protecting effects of FDP in crystalloid cardioplegic solution (St. Thomas formula, 10$^{\circ}C$, pH = 7.4) and reperfusate using isolated rat hearts in modified Langendorf apparatus by the parameters of preischemic and post reperfusing heart rate, time to first beat, occurance of arrhythmia, time to stabilization, and the rate of left ventricular pressure developing. Group A (n = 10), containing no FDP in cardioplegic and reperfusing solutions was control. Group B (n = 5), containing FDP in cardioplegic solution, showed statistically significant superiority of postischemic left ventricular pressure development than the control group. Group C (n = 5), containing FDP in reperfusate, showed statistically significant myocardial depressing effect than the controls. Other parameters were unremarkable. The cause is uncertain, but it is assumed that the negative feedback inhibition of FDP in energy metabolism or unknown blocking effect of FDP on certain transmembrane ionic currents is present. In conclusion, 1) FDP in cardioplegic solution has beneficial effect on postischemic left ventricular preservation. 2) FDP is strong acid when is hydrolyzed, so precise acid titration is neccessary. 3) FDP in reperfusate has negative left ventricular preservation, otherwise the mechanism is still uncertain.

• 대한한의학회지
• /
• 제23권2호
• /
• pp.164-179
• /
• 2002

Object: Death rate due to hypertension, atherosclerosis, ischemic heart disease and cerebral infarction induced by Westernized diet and increased average life span is on the rise. Decrease in blood circulation, activation of thrombus generation and intravascular lipid accumulation, cited as the principal causes of the above mentioned diseases in recent studies, result in circulatory disturbance and blood vessel obstruction leading to ischemic cell death of heart, brain and peripheral vessels. Method: We investigated the biochemical changes in microvascular permeability, aggregation of platelet and the intravascular lipid accumulation in induced-diabetic rat using Streptozotocin. We also studied the effects of Woohwangcheongsirn-won after oral administration on blood circulation, platelet function and lipid metabolism. The results are as follows: I. Woohwangcheongsim-won increased blood circulation in microvessels. 2. Woohwangcheongsim-won increased the reduced erythrocyte deformability in diabetes. 3. Woohwangcheongsim-won induced the reduction of contents of 2, 3-DPG, but failed to affect the reduced contents of ATP in erythrocyte in diabetes. 4. Woohwangcheongsim-won reduced the activity of Ca/sup 2+/-ATPase in the membrane of erythrocyte. 5. Woohwangcheongsim-won reduced the platelet aggregation evoked by platelet agglutinin factor. 6. Woohwangcheongsim-won reduced the production of platelet-derived granules. 7. Woohwangcheongsim-won reduced the production of metabolites of arachidonic acid in diabetes, and also reduced the production of increased thromboxane B2. 8. Woohwangcheongsim-won reduced the synthesis of oxidized LDL-cholesterol. In conclusion, Woohwangcheongsim-won enhanced blood circulation in microvesseles, erythrocyte deformability and inhibited the increased platelet aggregation and the synthesis of oxidized LDL-cholesterol in diabetes. Therefore Woohwangcheongsim-won is believed to positively affect blood circulation (J Korean Oriental Med 2002;23(2):164-179)

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권2호
• /
• pp.175-182
• /
• 1999

In the present study, the underlying mechanisms for diabetic functional derangement and insulin effect on diabetic cardiomyopathy were investigated with respect to sarcoplasmic reticulum (SR) $Ca^{2+}-ATPase$ and phospholamban at the transcriptional and translational levels. The maximal $Ca^{2+}$ uptake and the affinity of $Ca^{2+}-ATPase$ for $Ca^{2+}$ were decreased in streptozotocin-induced diabetic rat cardiac SR, however, even minimal amount of insulin could reverse both parameters. Levels of both mRNA and protein of phospholamban were significantly increased in diabetic rat hearts, whereas the mRNA and protein levels of SR $Ca^{2+}-ATPase$ were significantly decreased. In case of phospholamban, insulin treatment reverses these parameters to normal levels. Minimal amount of insulin could reverse the protein levels; however, it could not reverse the mRNA level of SR $Ca^{2+}-ATPase$ at all. Thus, the decreased SR $Ca^{2+}$ uptake appear to be largely attributed to the decreased SR $Ca^{2+}-ATPase$ level, which is further impaired due to the inhibition by the increased level of phospholamban. These results indicate that insulin is involved in the control of intracellular $Ca^{2+}$ in the cardiomyocyte through multiple target proteins via multiple mechanisms for the decrease in the mRNA for both SR $Ca^{2+}-ATPase$ and phospholamban which are unknown and needs further study.

• 한국동물위생학회지
• /
• 제33권3호
• /
• pp.303-307
• /
• 2010

The aim of this study was to determine the effects of body weight, organ weight, hematological values and biochemical parameters by estrogen on the ovariectomized (OVX) rats. The animals were divided into 4 groups. Intact group (n=10) received no treatment and operation. Sham group (n=10) received only sham operation and no treatment. OVX group (n=10) received operation and no treatment. OVX+E2(n=10) received operation and estrogen. The body weight of each group increased, but that of OVX+E2 group decreased. There were very significant differences (P<0.001) of body weights between OVX+E2 group and the other groups. Also, the wight of important organs such as heart, liver, spleen and kidney was measured. The heart weight was significantly lower(P<0.05) in the OVX+E2 group than the Intact group. The liver weight of the OVX+E2 group was significantly different in comparison with those of the other groups. On the other hand, there were no significantly differences in the organ weight of spleen and kidney between the OVX+E2 group and the other remaining groups. The hematological values of WBC, RBC, MeV, MCH and MCHC were not significantly different among the groups. The serum total protein and albumin decreased significantly in the OVX+E2 group as compared to those in the intact group. But, there were no significant differences in Ca, IP and Mg among the groups. We conclude that estrogen was significantly decreased the body weight in the ovariectomized rats. Our findings suggest that estrogen may influence the process of lipid packaging and absorption in the ovariectomized rats.

• Journal of Chest Surgery
• /
• 제31권9호
• /
• pp.845-854
• /
• 1998

Background: S-2-(3 aminoprophlamino) ethylphosphorothioic acid(WR-2721) is one of the radical scavenging thiols. We tested its protective effects in the reperfused heart. Material and Method: The experimental setup was the constant pressure Langendorffs perfusion system. We investigated the radical scavenging properties of this compound in isolated rat hearts which were exposed to 20 minutes ischemia and 20 minutes reperfusion. Four experimental groups were used:group I, control, Amifostine 50 mg(1 mL) peritoneal injection 30 minutes before ischemia(group II), Amifostine 10 mg(0.2 mL) injection during ischemia through coronary artery(group III),and Amifostine 50 mg(1 mL) peritoneal injection 2 hrs before ischemia(group IV). The experimental parameters were the levels of latate, CK-MB, and adenosine deaminase(ADA) in frozen myocardium, the quantity of coronary flow,and left ventricular developed pressure, and it's dp/dt. Statistical analysis was performed using repeated measured analysis of variance and student t-test. Result: The coronary flow of group II and IV were less than group I and III at equilibrium state but recovery of coronary flow at reperfusion state of group II, III, and IV were more increased compared with group I. The change of systolic left ventricular devoloping pressure of group II and IV were less than control group at equilibrium state, which seemed to be the influence of the pharmacological hypotensive effect of amifostine. But it was higher compared with group I at reperfusion state. The lactic acid contents of group II were less than control group in frozen myocardium.(Group I was 0.20 0.29 mM/g vs Group II, which was 0.10 0.11 mM/g). The quantity of CK-MB in myocardial tissue was highest in group IV (P=0.026 I: 120.0 97.8 U/L vs IV: 242.2 79.15 U/L). The adenosine deaminase contents in the coronary flow and frozen myocardium were not significantly different among each group. Conclusion: Amifostine seemed to have significant cardioprotective effect during ischemia and reperfusion injuries of myocardium.

• Biomolecules & Therapeutics
• /
• 제20권4호
• /
• pp.386-392
• /
• 2012

The endothelin (ET) signaling pathway controls many physiological processes in myocardium and often becomes upregulated in heart diseases. The aim of the present study was to investigate the effects of ET receptor upregulation on the contractile function of adult ventricular myocytes. Primary cultured adult rat ventricular myocytes were used as a model system of ET receptor overexpression in the heart. Endothelin receptor type A ($ET_A$) or type B ($ET_B$) was overexpressed by Adenoviral infection, and the twitch responses of infected ventricular myocytes were measured after ET-1 stimulation. Overexpression of $ET_A$ exaggerated positive inotropic effect (PIE) and diastolic shortening of ET-1, and induced a new twitch response including twitch broadening. On the contrary, overexpression of $ET_B$ increased PIE of ET-1, but did not affect other two twitch responses. Control myocytes expressing endogenous receptors showed a parallel increase in twitch amplitude and systolic $Ca^{2+}$ in response to ET-1. However, intracellular $Ca^{2+}$ did not change in proportion to the changes in contractility in myocytes overexpressing $ET_A$. Overexpression of $ET_A$ enhanced both systolic and diastolic contractility without parallel changes in $Ca^{2+}$. Differential regulation of this nature indicates that upregulation of $ET_A$ may contribute to diastolic myocardial dysfunction by selectively targeting myofilament proteins that regulate resting cell length, twitch duration and responsiveness to prevailing $Ca^{2+}$.