Autophagic vacuoles

We have recently shown, in Seg-1 cells derived from a patient with esophageal adenocarcinoma, that bile acids and low pH induce the dramatic formation of autophagic vacuoles (unpublished data). We also showed that persistent treatment of Het-IA cells (derived from normal human esophageal squamous epithelium) with a bile-acid cocktail and low pH resulted in the development of mutated clones that contain a partly duplicated chromosome 16 (unpublished data from a CGH microarray). In addition to other protective genes, this chromosome 16 duplication resulted in the duplication of the major ATPase necessary for the acidification of vesicles associated with the autophagic process. 

Dunn, W. A. (1990). Studies on the mechanisms of autophagy Formation of the autophagic vacuole. /. Cell Biol. 110,1923-1933. 

Mouse L pictor Laborious movement and ataxia Single-cell necrosis in file heart. Autophagic vacuoles in proximal convoluted tubules of file kidney. Glommili normal. Vacuolation and fat d osition in midzonal hepatocytes. Autophagic vacuoles in pancreatic acinar cells. Vacuolation in intestinal epithelium [93]... 

Addition of proteinase inhibitors to cells or their injection in vivo not only inhibits lysosomal proteinase activities but also causes formation of autophagic vacuoles 115) and induces synthesis of hemoglobinhydrolyzing thiol proteinase 16, 63). Increase of autophagic vacuoles in cells by treatment with leupeptin is responsible for inhibition of lysosomal thiol proteinase activities with consequent decrease of protein degradation. 

Recent studies indicated that the rate of sequestration of substrate proteins into the autophagic vacuoles may be the rate-limiting step in the process of protein degradation, and that lysosomal proteinases, especially thiol proteinases, exist in excess and may not be the rate-limiting step. 

Structure, function and turnover of autophagic vacuoles have been studied biochemically after enrichment of the organelles by cell fractionation... 

Alveolar macrophages obtained by bronchoalveolar lavage from 25 silicotic patients under the electron microscope showed silica particles, activated nuclei, autophagic vacuoles and destroyed cell organelles (Reisz et al. 1988). Lysosomal acid phosphatase activity was elevated as compared with healthy volunteers. 

Fig. 253. Autophagic vacuoles in the intermittent hypoxic neurohypophyseal secretory neurones (block 1330) of a rat (No. 11) treated for 8 consecutive days with intraperitoneal injection of 15 mg carbocromene per kg body weight x day. On the last 5 days of experimentation the animal was exposed to an atmosphere containing only 5 % oxygen for 30 min. On August 5, 1976 half an hour after the last exposure, under pentobarbital anaesthesia (30 mg/kg), the animal was perfused from the abdominal aorta with 2.5 % glutaraldehyde in 0.1 M sodium cacodylate buffer (pH 7.4). Postfixation with 1 % osmium tetroxide in sodium cacodylate buffer. Embedded in Epon 812 and sectioned at 50 nm. Lead citrate and uranyl acetate. Plate 3461...

The IBM autophagic vacuoles, which typically contain membranous debris, appear to be lysosomal, and to be a result of musde-fiber destruction [2, 7]... 

Although autophagic vacuoles associated with accumulated lysosomal-membranous structures in s-IBM muscle biopsies (Figure 7.2) have been known for many years ([169-171] and recently reviewed in [2, 7, 172]), the mechanism of... 

In addition to activated macroautophagy, our studies provided important evidence that autophagy related to lysosomal function is impaired in s-IBM muscle fibers. They showed a decrease of lysosomal cathepsin D and B enzymatic activities that appeared spedfic to s-IBM, because in polymyositis muscle fibers their activities were actually increased in our study [13] and in studies by others (referenced in [13]). In polymyositis macroautophagy was also increased but autophagic vacuoles and indusions do not form, perhaps because the lysosomal system may be functioning adequately. Our results also suggest that lymphocytic inflammation, which is... 

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