Distribution of Neuronal Apoptosis Inhibitory Protein in Human Tissues

Abstract

The neuronal apoptosis inhibitory protein (NAIP) gene, also known as the baculovirus inhibitor of apoptosis repeat-containing protein 1 (BIRC1) gene, is a member of the inhibitors of apoptosis (IAP) family and was first characterized as a candidate gene for spinal muscular atrophy (SMA). The expression of NAIP has been thoroughly studied in the central nervous system and overlaps the pattern of neurodegeneration in SMA. Recent studies have pointed to a role for NAIP in non-neuronal cells. We report here the production of a specific anti-NAIP antibody and the profile of NAIP expression in human adult tissues by Western blot and immunohistochemical detection methods. NAIP was detected in a number of tissues by Western blot analysis, but immunohistochemistry revealed that NAIP's presence in certain tissues, such as liver, lung, and spleen, is most likely due to macrophage infiltration. In the small intestine, the expression of NAIP coincides with the expression of p21WAF1. This observation, coupled with findings from other groups, suggests a role for NAIP in increasing the survival of cells undergoing terminal differentiation as well as the possibility that the protein serves as an intestinal pathogen recognition protein. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

Neuronal apoptosis inhibitory protein (NAIP) localizes to the cytokinetic machinery during cell division

“…An earlier study of NAIP distribution in human tissues36 showed a particularly intense staining in the small intestine epithelium. Based on these results, the further characterization of NAIP by confocal microscopy in the human epithelial carcinoma cell line HeLa, was undertaken and unexpectedly demonstrated the presence of NAIP in the central spindle (Fig.…”

“…Standardized amounts of protein samples (25  μ g to 50  μ g) were separated by 10% SDS-PAGE. Proteins were subsequently transferred onto nitrocellulose membrane and incubated in blocking solution (PBS, 5% nonfat milk, 0.2% Tween-20) for 1 hour at room temperature followed by overnight incubation with the NAIP-J236 rabbit polyclonal antibody at 4 °C diluted at 1:1500. Membranes were washed with PBS-T (PBS, and 0.2% Tween-20) 3 times followed by incubation with secondary antibody (anti-rabbit or mouse; Cell Signaling) for 1 hour at room temperature at the dilution suggested by the manufacturer.…”

The human apoptosis inhibitor NAIP induces pyroptosis in macrophages infected with Legionella pneumophila

“…It is plausible that mNaip5 binds to caspase-3 and -7 and/or uses procaspase-9 sequestration to block the activation of APAF-1 apoptosome, as human NAIP does [5,6]. Human NAIP is predominantly expressed in macrophage cells of the lung and spleen [30], suggesting that human NAIP protects macrophage cells from apoptotic cell death in these human tissues.…”

“…In human lung and spleen tissue, human NAIP is predominantly expressed in macrophage cells [30], suggesting that it is involved in their survival. This study demonstrates the dual role of human NAIP, and also of mNaip5, in macrophage survival, leading to cell death caused by L. pneumophila infection and protecting from apoptosis induced by DNA damage.…”

Pulse Probiotic Administration Induces Repeated Small Intestinal Muc3 Expression in Rats

“…NAIP is highly expressed in intestinal villi (23) and evidence is emerging for it being an intracellular pathogen receptor, chiefly for flagellin. Although none of bacteria in this study are flagellated, past work has shown NAIP modulation lies downstream of the TNF pathway (24) and it may be that probiotic modulation of TNF-␣ (25) elicited the IAP elevation observed in our animals.…”