Abstract
Immunohistochemistry (IHC) for detecting key signal molecules involved in programmed cell death (PCD) in archival human pathology specimens is fairly well established. Detection of cleaved caspase-3 in lymphocytes in rheumatoid arthritis (RA) and gastric surface foveolar glandular epithelia but not in synoviocytes in RA, gastric fundic glandular epithelia, or nasal NK/T-cell lymphoma (NKTCL) cells suggests anti-apoptotic mechanisms in cell differentiation and in oncogenesis such as the induction of survivin. Enzymatically pretreated and ultra-super sensitive detection of beclin-1 in synoviocytes in RA and gastric fundic glandular epithelia suggests enhanced autophagy. The deposition of beclin-1 in fibrinoid necrosis in RA and expression of beclin-1 in detached gastric fundic glandular cells suggest that enhanced autophagy undergoes autophagic cell death (ACD). NKTCL exhibited enhanced autophagy through LC3 labeling and showed densely LC3 labeled cell-debris in regions of peculiar necrosis without deposition of beclin-1, indicating massive ACD in NKTCL and the alternative pathway enhancing autophagy following autophagic vesicle nucleation. Autophagy progression was monitored by labeling aggregated mitochondria and cathepsin D. The cell-debris in massive ACD in NKTCL were positive for 8-hydroxydeoxyguanosine, suggesting DNA oxidation occurred in ACD. Immunohistochemical autophagy and PCD analysis in archival human pathology specimens may offer new insights into autophagy in humans.
Highlights
Recent molecular and cell biological research efforts have been rewarded by fruitful results and many antibodies against signal transduction molecules and their antagonists have been supplied commercially
Through developed antigen retrieval and immunohistochemistry (AR-IHC) using these antibodies, it becomes possible to label these signal transduction molecules and antagonists in archival formalin-fixed and paraffin-embedded human pathology specimens, a huge number of which have been collected in the so-called Department of Human Pathology
Comparative Antigen Retrieval (AR)-IHC using antibodies against the representative signal transduction molecules and antagonists in the archival human pathology specimens with and without various diseases is expected to be informative about differences in features of signal transduction between normal and diseased human cells in the tissues and to contribute to the medicine for the diseases and probably to further molecular and cell biological research
Summary
Recent molecular and cell biological research efforts have been rewarded by fruitful results and many antibodies against signal transduction molecules and their antagonists have been supplied commercially. Molecular mechanisms of autophagy and autophagic cell death (ACD), known as type II PCD [5,6,7,8], have been clarified [7,9,10,11,12,13]. Vps, and Vps for autophagic vesicle nucleation, and against LC3 (LC3-II), which localizes in the membrane of autophagosomes, are supplied commercially (Table 1) Using these antibodies, we performed AR-IHC on archival human pathology specimens for detecting autophagy [14,15,16]. We aimed to differentiate apoptosis, autophagic cell death (ACD) and other types of PCD using archival human pathology specimens. This paper reports on homeostatic mass control in the gastric fundic glandular mucosa with and without Helicobacter pylori (HP) [14] and peculiar necrosis in EpsteinBarr virus (EBV)-related nasal natural killer (NK)/T-cell lymphoma [15,16], and includes a discussion on the applications of AR-IHC for PCD in human pathology and autophagy research in humans
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