[Role and regulation of calcineurin-dependent signal pathway in cardiac hypertrophy of rats].

The present study investigated the role and regulation of calcineurin-dependent signal pathway in cardiac hypertrophy of rats from the three levels of animal model, culturing cells and molecular biology. The results showed as follows: (1) Calcineurin signal pathway involves in myocyte hypertrophy induced by various factors such as hemodynamic overload, myocardial fibrosis, paracrine/autocrine factors, etc.; (2) Calcineurin-dependent signal pathway plays an important role not only in AngII- and bFGF-induced cardiac myocyte hypertrophy but also in AngII- and bFGF-stimulated cardiac fibroblast proliferation. (3) Calcineurin pathway may associate with MAPK and PKC pathways at several levels; (4) Activation of calcineurin depends on sustained increase of intracellular calcium concentration and is regulated by protein phosphorylation. The expression of calcineurin gene in AngII-stimulated myocytes might be regulated by Ca2+ signal and MAPK cascade. In conclusion, Ca(2+)-calcineurin signal pathway involves in the development of cardiac hypertrophy of rats.

[Studies on the spectroscopic property of p-hydroxyphenol derivatives].

In the paper, properties of p-hydroxyphenol derivatives are described. The results prove that p-hydroxyphenol derivatives with different function groups show different spectroscopic properties. Some methods will be proposed to analyze a series of p-hydroxyphenol derivatives in blood or urine so as to identify the cancer mark.

Effect of batroxobin against dog heart ischemia/reperfusion injury.

AIM: To study the effect of batroxobin(Bat) on dog heart ischemia/reperfusion (I/R) injury. METHODS: Dog heart I/R injury was induced by occluding the left anterior descending coronary artery for 30 min and restoring blood perfusion for 90 min. Bat was intravenously injected before heart ischemia and 15 min before reperfusion. Plasma creatine kinase (CK), lactate dehydrogenase (LDH), and myocardial malondiaedehyde (MDA) concentrations were measured. The pathologic changes of I/R myocardium were observed. RESULTS: Bat reduced the mortality rate of I/R dog (I/R group 65.0% vs Bat-I group 30.0% and Bat-II group 28.6%, P < 0.05). Myocytes of I/R heart showed intracellular edema, damaged mitochondria, and concentrated nucleus. Bat decreased these changes. In Bat-I and Bat-II group, plasma CK and LDH level were reduced, the +dp/dtmax and -dp/dtmax at 30 min after ischemia and 90 min after reperfusion were elevated, and left ventricular end dilation pressure (LVEDP) was lowered. The myocardial MDA contents were decreased by 42.3% and 38.1% (P < 0.01) in Bat-I and Bat-II group, respectively. CONCLUSION: Bat may exert an apparent role against dog heart ischemia/reperfusion injury and improve myocardial function.

[Role of calcineurin in cardiac fibroblast proliferation stimulated by angiotensin II].

The present study was undertaken to observe the role of calcineurin (CaN) in the angiotensin II (Ang II) stimulated cardiac fibroblast proliferation. In cultured cardiac fibroblasts of neonatal rats, Ang II was used to stimulate proliferation while CaN was inhibited by CaN CsA inhibitor cyclosporin A (CsA). (3)H-TdR incorporation, activity of CaN and intracellular calcium concentration were measured. (3)H-TdR incorporation of Ang II stimulated fibroblasts was 72% higher than control (P<0.01), which was inhibited by CsA (0.1 10 micromol/L) in a dose dependent manner. Intracellular Ca(2+) level and CaN activity of Ang II stimulated fibroblasts were respectively 112% (P<0.01) and 17%(P<0.05) higher than control. It is concluded that CaN may play an important role in signal transduction of the Ang II induced cardiac fibroblast proliferation.

[Signal transduction pathways in cardiac myocyte hypertrophy].

Cardiac hypertrophy is the consequence of hypertrophic stimulus-induced changes in gene expression, which is linked by intracellular signal transduction. It is likely, however, that there are "molecular phenotypic" differences underlying cardiac hypertrophy triggered by different stimuli, which is caused by the different signal pathways that they initiated. Studying on the signal pathways in cardiac myocyte hypertrophy contributed to elucidate the cellular and molecular mechanisms of cardiac hypertrophy and might find some new strategies for the prevention of cardiac hypertrophy.

[Involvement of calcineurin-dependent signal pathway in the angiotensin II-induced cardiac myocyte hypertrophy].

The present study was undertaken to observe the role of calcineurin (CaN)-dependent signaling pathway in the angiotensin II (Ang II)-induced cardiac myocyte hypertrophy. In cultured myocardial cells of neonatal rats, Ang II was used to stimulate hypertrophy and CaN-pathway blocked by CsA(an inhibitor of CaN). 3H-leucine incorporation, and activities of CaN, mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) were investigated. The results showed that 3H-leucine incorporation of Ang II-stimulated myocardial cells was 46% higher than control (P < 0.01), which could be inhibited by CsA (0.5-5 micrograms/ml) and PD098059(an inhibitor of MAPK). CaN and PKC activities of Ang II-stimulated myocardial cells were 39% and 280% higher than control (P < 0.001) respectively, while no significant increase in MAPK activities was observed. CsA could reverse the increase of CaN activity, but had no effect on PKC. It is concluded that the CaN-dependent signaling pathway may play an important role in the development of the Ang II-induced cardiac myocyte hypertrophy.

[The role of endogenous CO in the regulation of endothelin-induced VSMC proliferation and MAPK activity].

Heme oxygenase (HO) is a rate-limiting enzyme of heme degradation, which converts the cellular heme to bilirubin and carbon monoxide (CO). Recently it is suggested that endogenous CO plays an important role in regulating vascular tone under both physiological and pathological conditions, but it is not clear whether endogenous HO/CO system regulates vascular smooth muscle cell (VSMC) proliferation. In the present study, VMSC 3H-TdR incorporation, mitogen-activated protein kinase (MAPK) activity, HO activity and CO release were determined to study the role of endogenous HO/CO system in regulating the VSMC proliferation induced by endothelin-1 (ET-1) in a cultured system. The results showed that ET-1 increased VSMC 3H-TdR incorporation, MAPK activity, HO activity, and CO release were up-regulated. Pretreatment of HO inhibitor, zinc protoporphyrin-9 (ZnPP-9), increased the ET-1-induced VSMC 3H-TdR incorporation and MAPK activity by 31.8% and 36.6% (P < 0.01, respectively), whereas pretreatment of heme-L-lysinate (HLL), a HO substrate, inhibited these activities. This study demonstrated that up-regulation of VSMC endogenous HO represents a cellular protective response to stress or injury. Inhibition of HO may enhance VSMC proliferation induced by ET-1 in vitro, suggesting that endogenous HO/CO system may be directly involved in the regulation of VSMC proliferation through MAPK signaling pathway.