Inhibition of Necroptosis in Acute Pancreatitis: Screening for RIPK1 Inhibitors

RIPK1 prevents aberrant ZBP1-initiated necroptosis

Receptor interacting protein kinase 1 (RIPK1) regulates inflammation and cell death, in host defense and homeostasis. The adaptor function of RIPK1 allows pro-survival and inflammatory signaling, while its kinase activity regulates the induction of necroptosis and apoptosis. A new level of regulation through its RIP homotypic interaction motif (RHIM) was recently discovered to suppress necropto...

Tyrosine kinase inhibitors and acute pancreatitis.

RIPK1 can function as an inhibitor rather than an initiator of RIPK3-dependent necroptosis.

Tumour necrosis factor and lipopolysaccharide can promote a regulated form of necrosis, called necroptosis, upon inhibition of caspase activity in cells expressing receptor-interacting serine/threonine kinase (RIPK)3. Because inhibitors of RIPK1 kinase activity such as necrostatin-1 block necroptosis in many settings, RIPK1 is thought to be required for activation of RIPK3, leading to necroptos...

Necroptosis is associated with low procaspase-8 and active RIPK1 and −3 in human glioma cells

Necroptosis is a regulated necrotic cell death that involves receptor-interacting protein kinases RIPK1 and RIPK3. Here, we report that edelfosine triggers a rapid and massive cell death in human glioblastoma cells with characteristics of necrosis. Only a minor proportion of edelfosine-treated cells underwent caspase-dependent apoptosis. Autophagy and a rapid influx of extracellular calcium int...

Necroptosis In Vivo Are Viable and Protected from TNF-Induced Cutting Edge: RIPK1 Kinase Inactive Mice