Caspase-4 Directly Activates Caspase-9 in Endoplasmic Reticulum Stress–Induced Apoptosis in SH-SY5Y Cells

Abstract

Abstract. The present study investigated the function of caspase-4 in endoplasmic reticulum (ER) stress-induced apoptosis in human neuronal cell line SH-SY5Y. Tunicamycin, which is known to induce ER stress, activated both caspase-9 and caspase-4, and the activation of caspase-4 preceded that of caspase-9. The caspase-4 inhibitor LEVD-CHO suppressed both the apoptosis and caspase-9 activation. In addition, human recombinant active caspase-4 cleaved wild type and D330A mutant substituted Asp-330 for alanine of human recombinant procaspase-9, but did not cleave D315A mutant substituted Asp-315 for alanine. These results suggest that caspase-4 directly activates caspase-9 by the processing of procaspase-9 at Asp-315 in ER stress-induced neuronal apoptosis.

Characterization of Cholix Toxin-induced Apoptosis in HeLa Cells

“…Among the three caspases in human cells, caspase-4 has been reported to be involved in not only inflammation but also endoplasmic reticulum (ER) stress-induced apoptosis (40). Mitochondriaindependent caspase-9 activation by caspase-4 was also reported recently by Yamamuro et al in studies of ER stressinduced apoptosis in SH-SY5Y cells (41). It was suspected that Cholix induces some ER stress in HeLa cells.…”

Transmembrane Protein 214 (TMEM214) Mediates Endoplasmic Reticulum Stress-induced Caspase 4 Enzyme Activation and Apoptosis

“…vious studies reveal that procaspase 4 is cleaved and activated during tunicamycin-or TG-induced ER stress in several cell types, including SK-N-SH, SH-SY5Y, and human retinal pigment epithelial cells (17,18,21). As shown in Fig.…”

Caspase-2 and JNK Activated by Saturated Fatty Acids are Not Involved in Apoptosis Induction but Modulate ER Stress in Human Pancreatic �-cells

“…However, except of specific population of African descendents, the human population does not possess functional caspase-12 [35]. Several lines of evidence indicate that caspase-2 [22,23,24,25] or caspase-4 [36,37] could substitute for caspase-12 in human cells but this hypothesis has not yet been tested in pancreatic β-cells. Our preliminary experiments did not point at a significant role of caspase-4 activation in stearic acid-induced apoptosis of NES2Y cells (data not shown).…”