Alterations of cardiac ERK1/2 expression and activity due to volume overload were attenuated by the blockade of RAS.

The activities and protein content of extracellular signal-regulated kinase (ERK)1/2 in the heart were measured in rats at 4 and 16 weeks after volume overload due to aortocaval shunt. Protein content of phosphorylated ERK1/2 was increased at both 4 and 16 weeks, whereas protein content of total ERK1/2 was increased only at 16 weeks of inducing volume overload. The ERK1/2 activities, estimated as phospho-Elk-1 content, were also increased at 4 and 16 weeks of inducing volume overload. The increased phosphorylated ERK1/2 and E-26-like (Elk)-1 protein content in 16 weeks failing hearts was much greater than that in 4 weeks hypertrophied hearts. These changes in phosphorylated ERK1/2 and Elk-1 protein content in both 4 and 16 weeks volume overloaded animals were attenuated by treatment with enalapril and/or losartan. The results indicate that activation of ERK1/2 may be involved in the development of cardiac hypertrophy and heart failure due to volume overload, and these changes are partially prevented by blockade of the renin-angiotensin system (RAS).

Phospholipid profile of developing heart of rats exposed to low-protein diet in pregnancy.

Although the myocardial phospholipid and fatty acid content have profound effects on the heart function, very little information is available on the effects of restricted maternal protein intake during pregnancy on the phospholipid profile and fatty acid content of the developing heart. The present study was therefore undertaken to examine the effect of pregnant dams fed diets containing either 180 (normal) or 90 (low) g/kg casein diet for 2 wk before mating and throughout pregnancy on myocardial phospholipid and fatty acid content of male offspring. Whereas no changes in phosphatidylcholine and phosphatidylethanolamine were detected, increases in lysophosphatidylcholine, phosphatidylserine, and sphingomyelin were seen in the hearts of offspring in the low-protein (LP) group. Analysis of cardiac fatty acids revealed that although the saturated fatty acid (myristate, palmitate, and stearate) levels were significantly reduced, the unsaturated fatty acid (linoleate, arachidonate, and decosahexanoate) levels were significantly increased in the developing heart in the LP group. Furthermore, assessment of nuclear transcription factors involved in regulation of cardiac metabolism revealed a decrease in myocyte enhancer factor-2C mRNA levels in the LP group, whereas an increase in the mRNA amount of peroxisome proliferator-activated receptor-alpha was observed in this group. These results demonstrate that maternal LP diet can induce changes in the phospholipid profile and fatty acid content of the developing heart, which may have implications for metabolism of the neonatal heart.

Role of mitogen-activated protein kinase in cardiac hypertrophy and heart failure.

BACKGROUND: Mitogen-activated protein kinases (MAPKs) are involved in the regulation of various cellular responses including cell proliferation, differentiation and survival. Although MAPKs are activated by MAPK kinase and inactivated by phosphatases, different types of MAPKs, including extracellular signal-regulated kinases (ERK1 and 2), c-jun N-terminal protein kinases (JNK) and p38 kinases are known to participate in different signalling pathways. This article will review some salient features of the regulation and function of different forms of MAPKs in the heart. Furthermore, the status of cardiac MAPKs under different pathophysiological conditions will be described. OBSERVATIONS: A wide variety of external stimuli are known to activate MAPKs, which are then translocated from the cytoplasm to the nucleus and regulate cardiac gene expression by phosphorylating various transcriptional factors. By virtue of the involvement of ERK1/2 in hypertrophic response and of the stress-activated JNKs and p38 kinases in the process of apoptosis, MAPKs are considered to be intimately involved in cardiac remodelling. Both growth factors and phorbol esters have been shown to strongly activate ERK1/2, whereas the activation of JNKs and p38 kinases by these agents is weak. Although ischemia-reperfusion activates all types of MAPKs, JNKs and p38 kinases are mainly proapoptotic, whereas ERK1/2 are antiapoptotic. CONCLUSIONS: The activation of ERK1/2 is involved in signal transduction pathways associated with cardiac hypertrophy; however, the exact status of MAPKs in heart failure remains to be clearly defined. While both JNKs and p38 kinases appear to participate in the genesis of ischemia-reperfusion injury, ERK1/2 are considered to be cytoprotective.

In situ heparin-induced peroxisomal reticulum and biogenesis of peroxisomes in pulmonary intravascular macrophages (PIMs) of caprine lung: an ultrastructural and cytochemical study.

Pulmonary intravascular macrophages (PIMs) contain a unique electron-dense globular surface-coat which is sensitive to heparin treatment, halothane anesthesia, and the digestive effect of lipolytic lipase (LPL), suggesting that the coat is predominantly composed of lipoproteins. In the present study, evidence is presented that heparin, when administered intravenously in goats, potentiated both the translocation of the surface-coat into the vacuolar system and the expansion of the Golgi apparatus. Sequentially, these changes were followed by proliferation of peroxisomes in combination with peroxisomal reticulum (PR), a transient precursor of this organelle. The peroxisomes, as well as PR, reacted positively for catalase after aldehyde fixation and 3,3'-diaminobenzidine (DAB) staining. In addition to their role as phagocytes, the ultrastructural and cytochemical detection of peroxisomes suggests a functional capacity of the PIMs, which may be adaptable to the circulating level of free fatty acids (FAAs).