Morphology of mitochondrial permeability transition: morphometric volumetry in apoptotic cells.

Here we report on the mitochondrial permeability transition (MPT), which refers to the morphology of mitochondria whose inner membrane has lost its selective permeability. In all types of apoptotic cells so far examined, we found outer mitochondrial membranes that had been ruptured. These mitochondria present a swollen matrix covered by an inner membrane herniating into the cytoplasm through the breached outer membrane. Similarly ruptured outer mitochondrial membranes have been reported in studies on mitochondrial fractions induced to undergo MPT, carried out by others. Our observations were made on five types of rat tissue cells and six different cultured cell lines in the early stages of apoptosis. Samples from the cell lines HL-60, HeLa, WEHI-164, and a special batch of PC-12 cells were subjected to various apoptogenic agents and analyzed morphometrically. Nonapoptotic companion cells with unaltered nuclear structure (CUNS) were also analyzed. The mitochondrial volume in microm(3) and the volume fraction of the cytoplasm occupied by mitochondria in cells with typical nuclear signs of apoptosis and also in CUNS were evaluated. The volume of the mitochondria with ruptured membrane represents at least 69% (47-89%) of the total mitochondrial volume of the apoptotic cells. Thus, a considerable fraction of the cellular mitochondrial mass is or was in the state of permeability transition and probably involved in enhancement of the apoptotic program. In all samples, a fraction of the cells with normal nuclei possessed mitochondria with breached outer membranes as described above. In these cells, MPT occurred before the appearance of the typical nuclear phenotype of the apoptotic cells.

Ventricular expression of atrial natriuretic peptide in chronic chagasic cardiomyopathy is not induced by myocarditis.

BACKGROUND: The ventricles of the normal heart are virtually devoid of atrial natriuretic peptide (ANP). Although ANP occurs in ventricles submitted to elevated wall stress, it is not clear whether ANP expression is affected by myocarditis. We investigated the immunohistochemical expression of ANP in chronic chagasic cardiomyopathy, an inflammatory cardiomyopathy caused by infection with the protozoan Trypanosoma cruzi. METHODS: Necropsy samples from the left and right ventricles of 16 patients exhibiting chronic chagasic cardiomyopathy were evaluated for myocarditis, fibrosis, T. cruzi parasites and ANP immunoreactivity. The diameters of 50 myocytes per sample were measured. RESULTS: ANP was present in myocytes of the subendocardial region in 13/16 (81.3%) left and 10/16 (62.5%) right ventricular samples (P=0.25). Myocytes present in the inflammatory foci, near the infiltrating inflammatory cells but distant from the subendocardial region, did not express ANP. Trypanosoma cruzi parasites exhibited intense immunoreactivity for ANP. The mean myocyte diameter and the incidence of myocarditis, fibrosis, and T. cruzi parasites was similar between the left and right ventricular samples. No statistical differences were found between the ANP-positive and ANP-negative cases. CONCLUSIONS: In chronic chagasic cardiomyopathy, both ventricles exhibit hypertrophy, fibrosis and ANP in the subendocardial region. The inflammatory infiltrate does not induce ANP expression in the myocytes. Regional stress but not myocarditis itself, is probably responsible for ventricular ANP expression in myocarditis.