‘Senescence‐associated’ β‐galactosidase activity in the upper gastrointestinal tract

Abstract

Beta-galactosidase activity at pH 6 is associated in vitro with senescence and cellular death, but in vivo data are sparse. This study undertook firstly to map 'senescence-associated' beta-galactosidase activity (SAbetaG) at pH 6 in normal epithelia and mucosae of the upper gastrointestinal tract. As escape from senescence confers a proliferative advantage, a reduction in SAbetaG activity might be predicted in neoplasia and their precursors in vivo. This prediction was tested in metaplastic, dysplastic, and neoplastic epithelium of the upper gastrointestinal tract. Histochemical staining for SAbetaG was performed at pH 6 on cryostat sections of 350 endoscopic biopsies from sites including oesophagus, stomach, and duodenum of 46 patients: 28 with Barrett's oesophagus (two with adenocarcinoma), 15 with gastric adenocarcinoma, and three with oesophageal squamous cancer. A staining score (range 0-6) was assigned to epithelial cells in all mucosae and scores were calculated for surface (luminal), intermediate, and deep (basal) layers. The strongest SAbetaG activity was in surface luminal cells of normal duodenal mucosa (mean score 3.6+/-0.5; n=19), 'specialized' Barrett's mucosa (mean 2.2+/-0.12; n=105), and intestinal metaplasia in the stomach (mean 2.4+/-0.40; n=16). Squamous epithelium was consistently negative for SAbetaG activity. Low- and high-grade Barrett's dysplasia showed no decrease in SAbetaG activity, but reduced activity was seen in gastric and oesophageal adenocarcinomas (mean 1.24+/-0.29; n=17; p=0.012). In six gastric adenocarcinomas, there was no detectable activity. Whether SAbetaG is truly a marker of cellular senescence in vivo remains to be determined. Activity is low in mucosal proliferation compartments and increases with cellular differentiation, especially in native or metaplastic intestinal mucosae. SAbetaG activity persists in dysplastic mucosae but may show some reduction or loss in adenocarcinomas (p=0.0012). Loss of SAbetaG activity is not, therefore, an early event in glandular dysplasia-neoplasia of the upper gastrointestinal tract.

Hyperactivation of Ha-ras oncogene, but not Ink4a/Arf deficiency, triggers bladder tumorigenesis

“…Despite the significant upregulation of several senescence-associated molecules, histological evidence of cellular senescence was not observed in Ha-ras-expressing urothelial cells, as indicated by the lack of enzyme activity of senescence-associated β-galactosidase in any of the urothelial lesions examined ( Figure 1D; ref. 43). Therefore, it appears that both the spectrum of affected senescence-associated molecules and the biological consequences of ras activation are cell type dependent.…”

“…Control experiments were carried out simultaneously using adjacent sections to detect non-senescence-associated β-galactosidase activity with the same solution made in acidic pH (4.0; ref. 43). The sections were counterstained with 1% neutral red and examined by light microscopy.…”

Anti-aging Effects of Cyanidin under a Stress-Induced Premature Senescence Cellular System

“…In particular, b-galactosidase activity in human fibroblasts at pH 6 is a well-known senescence marker, and elevation of b-galactosidase activity in long-term non-proliferating cells may be considered as the manifestation of a high level of catabolism and perhaps forthcoming cell death. 45,46) Therefore, further study is needed to clearly explain the effects of cyanidin on cellular aging.…”

The essence of senescence: Figure 1.

“…In addition to senescent cells, contact-inhibited or serumstarved cells in tissue culture, as well as proliferating dysplastic epithelium in the gastrointestinal tract, can be positive for SA-b-GAL (Severino et al 2000;Going et al 2002;Yang and Hu 2005). Furthermore, one would expect that increases in the number or activity of lysosomes unrelated to senescence would also result in elevated lysosomal b-galactosidase protein levels, and thus in increased SA-b-GAL activity.…”