Engulfment of Apoptotic Cells in C. elegans Is Mediated by Integrin α/SRC Signaling

SummaryBackgroundEngulfment of apoptotic cells is important for cellular homeostasis and the development of multicellular organisms. Previous studies have shown that more than one engulfment receptors act upstream of the conserved signaling module CED-2/CrkII-CED-5/Dock180-CED-12/ELMO for cell corpse removal in C. elegans, but little is known about their identities, except for PSR-1.ResultsWe show that in C. elegans, integrin functions as an engulfment receptor in the recognition and subsequent phagocytosis of apoptotic cells. Mutations in the integrin α gene ina-1 result in inefficient engulfment of apoptotic cells. The INA-1 extracellular domain binds to the surface of apoptotic cells in vivo. This binding requires the phospholipid scramblase SCRM-1, which promotes the exposure of phosphatidylserine, a key “eat me” signal in apoptotic cells. Furthermore, we identify an essential role of the nonreceptor tyrosine kinase SRC-1 in INA-1-mediated cell corpse removal. INA-1 and SRC-1 both act in the engulfing cells during the engulfment process and are colocalized in the phagocytic cups extending around apoptotic cells. Finally, our genetic and biochemical data suggest that SRC-1 relays the scrm-1-dependent engulfment signal from INA-1 to the conserved motility-promoting signaling complex CED-2/CrkII-CED-5/Dock180-CED-12/ELMO for CED-10/Rac activation, probably by interactions with CED-2 and the INA-1 cytoplasmic domain, leading to the internalization of apoptotic cells.ConclusionsOur findings provide evidence that integrin functions as an engulfment receptor at the whole-organism level and reveal a nonconventional signaling pathway in which SRC provides a FAK-independent linkage between integrin α and the common motility-promoting signaling module CED-2/CrkII-CED-5/Dock180-CED-12/ELMO to promote the internalization of apoptotic cells

Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH 2

Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts proliferation and extracellular matrix accumulation. Induction of fibroblast apoptosis therefore plays a crucial role in the resolution of this disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic compound, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic acid. We found that treatment with gallic acid resulted in activation of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts. Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and Fas expression, and abolished apoptosis induced by gallic acid. Moreover, treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase) effectively diminished gallic acid-induced hydrogen peroxide production, JNK and p53 activation, and cell death. These observations imply that gallic acid-mediated hydrogen peroxide formation acts as an initiator of JNK signaling pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts

Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70 kDa U1-snRNP autoantigen

<p>Abstract</p> <p>Background</p> <p>Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders. Although we have previously reported that B19 non-structural protein (NS1) induces mitochondrial-dependent apoptosis in COS-7 cells, the precise mechanism of B19-NS1 in developing autoimmunity is still obscure.</p> <p>Methods</p> <p>To further examine the effect of B19-NS1 in presence of autoantigens, COS-7 cells were transfected with pEGFP, pEGFP-B19-NS1 and pEGFP-NS1K334E, a mutant form of B19-NS1, and detected the expressions of autoantigens by various autoantibodies against Sm, U1 small nuclear ribonucleoprotein (U1-snRNP), SSA/Ro, SSB/La, Scl-70, Jo-1, Ku, and centromere protein (CENP) A/B by using Immunoblotting.</p> <p>Results</p> <p>Significantly increased apoptosis was detected in COS-7 cells transfected with pEGFP-B19-NS1 compared to those transfected with pEGFP. Meanwhile, the apoptotic 70 kDa U1-snRNP protein in COS-7 cells transfected with pEGFP-B19-NS1 is cleaved by caspase-3 and converted into a specific 40 kDa product, which were recognized by anti-U1-snRNP autoantibody. In contrast, significantly decreased apoptosis and cleaved 40 kDa product were observed in COS-7 cells transfected with pEGFP-NS1K334E compared to those transfected with pEGFP-B19-NS1.</p> <p>Conclusions</p> <p>These findings suggested crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP.</p

Microwave Components with MEMS Switches

RF MEMS switches with metal-metal contacts are being developed for microwave applications where broadband, high linearity performance is required. These switches provide less than 0.2 dB insertion loss through 40 GHz. This paper describes the integration of these switches into selected microwave components such as reconfigurable antenna elements, tunable filters, switched delay lines, and SPDT switches. Microwave and millimeter wave measured results from these circuits are presented