The effects of MAPK inhibitors on antimycin A-treated calf pulmonary arterial endothelial cells in relation to cell death, reactive oxygen species and glutathione.

Antimycin A (AMA) inhibits succinate oxidase and the mitochondrial electron transport chain between cytochrome b and c. Here, we report on the effects of mitogen-activated protein kinase (MAPK) inhibitors on AMA-treated calf pulmonary artery endothelial cells (CPAEC) in relation to cell death, reactive oxygen species (ROS) and glutathione (GSH). AMA inhibited the growth of CPAEC and also induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm). AMA increased ROS levels including O2·-, and depleted GSH cell numbers in CPAEC. All the MAPK (MEK, JNK, p38) inhibitors enhanced cell growth inhibition and death by AMA, and appeared to augment ROS but not O2·- levels in AMA-treated CPAEC. MEK and p38 inhibitors did not increase the number of GSH-depleted cells in AMA-treated CPAEC, but JNK inhibitor significantly did. Each MAPK inhibitor affected cell growth, death, ROS and GSH levels differently in comparison to control CPAEC. In conclusion, the MAPK inhibitors enhanced cell growth inhibition and death by AMA. Changes in ROS and GSH levels by AMA and/or MAPK inhibitors affected growth and death in CPAEC.

Enhancement of propyl gallate-induced calf pulmonary arterial endothelial cell death by MEK and JNK inhibitors.

Propyl gallate (PG), a synthetic antioxidant, exerts a variety of effects on tissue and cell functions. Here, we investigated the effect of mitogen-activated protein kinase (MAPK) inhibitors on PG-treated calf pulmonary artery endothelial cells (CPAECs) in relation to changes in cell death, reactive oxygen species (ROS) and glutathione (GSH). PG inhibited CPAEC growth at 24 h and induced cell death, which was accompanied by the loss of mitochondrial membrane potential. PG also increased ROS levels in the CPAECs, while GSH depleted cell number. Treatment with MAPK (MEK, JNK and p38) inhibitors resulted in the slight enhancement of cell growth inhibition by PG. MEK and JNK inhibitors increased cell death and GSH depletion in PG-treated CPAECs without affecting ROS levels. In conclusion, PG inhibited the growth of CPAECs by regulating GSH levels. The pro-apoptotic effect of MEK and JNK inhibitors on PG-induced CPAEC death was related to a decrease in GSH levels.

Relationship of plasma Dendroaspis natriuretic peptide-like immunoreactivity and echocardiographic parameters in chronic haemodialysis patients.

BACKGROUND AND AIMS: The Dendroaspis natriuretic peptide (DNP), which was recently isolated from the venom of the green Mamba snake, Dendroaspis angusticeps, is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure. The purpose of this study was to evaluate the effect of haemodialysis (HD) on the plasma concentration of DNP, and to investigate the relationship between the 2-D echocardiographic parameters and the changes in the plasma DNP levels during HD. METHODS: Forty-five haemodialysis patients and 22 healthy individuals underwent a measurement of plasma DNP-like immunoreactivity, serum creatinine, haematocrit, blood pressure and bodyweight before and after each HD session. Echocardiography was performed before and after HD. The peak early diastolic transmitral flow velocity (E), peak late diastolic transmitral flow velocity (A), and E/A ratio were measured by using a pulsed Doppler echocardiogram. RESULTS: The plasma DNP-like immunoreactivity of those in the pre-HD state was significantly higher (235.6 +/- 45.8 pg/mL) than those of the healthy subjects (105.3 +/- 31.1 pg/mL). In addition, the plasma DNP-like immunoreactivity was significantly decreased after HD (204.4 +/- 55.4 pg/mL). The left atrial diameter, left ventricular diameter at end diastole and end systol, E velocity, A velocity, E/A ratio and inferior vena cava diameter were significantly decreased after HD. There were significant correlations between the changes of plasma DNP-like immunoreactivity and the changes in the bodyweight and inferior vena cava diameter, respectively. CONCLUSION: These results suggest that the plasma DNP-like immunoreactivity might be involved in the regulation of the blood volume in patients undergoing HD.