The translocation of HMGB1 during cell activation and cell death

Abstract

High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein with alarmin activity. When present in an extracellular location, HMGB1 can activate the innate immune system and promote inflammation in conditions such as sepsis. To exert these activities, HMGB1 must transit from the nucleus, through the cytoplasm, to the outside of the cell. This process can occur during cell activation as well as cell death. In murine macrophages (MPhi), stimulation of TLR3 and TLR4, but not TLR9, can cause HMGB1 translocation. With cell death, necrosis can lead to extracellular HMGB1 by a passive mechanism. With apoptosis, HMGB1 is only released during secondary necrosis, when cell permeability barriers break down. Since agents that stimulate MPhi can also induce apoptosis, HMGB1 release following TLR stimulation may also reflect a contribution from dead cells, suggesting a common mechanism for protein release in activation and death.

High Mobility Group Box 1 Protein Is Methylated and Transported to Cytoplasm in Clear Cell Renal Cell Carcinoma

“…Although a great deal of studies have reported roles of HMGB1 in oncogenesis, few reported the mechanisms of its cytoplasmic translocation and extracellular secretion. There is now a general consensus that cytoplasmic translocation is the precondition of extracellular secretion (Gauley et al, 2009). And it is safe to say that post translational modifications play an important role in the nucleocytoplasmic redistribution.…”

Phosphatidylinositol 3-kinases pathway mediates lung caspase-1 activation and high mobility group box 1 production in a toluene-diisocyanate induced murine asthma model

“…These processes can occur during cell activation as well as cell death. So it is regarded as a critical regulator of innate immunity (Castiglioni et al, 2011;Gauley and Pisetsky, 2009;Harris and Raucci, 2006). Recently, higher level of HMGB1 has also been reported to be associated with impaired lung function and more severe disease in subjects with asthma (Hou et al, 2011;Watanabe et al, 2011).…”

Efeitos do ácido docosahexaenoico (DHA) e do ácido araquidônico (AA) sobre a morte celular da linhagem celular de câncer de mama MDA-MB-231

“…A secreção de HMGB1 ocorre após a ativação da caspase 1 por diferentes inflamassomas (28) e a translocação dessa proteína do núcleo para o citoplasma é um evento necessário para a sua posterior secreção em células imunológicas (28,50). Nossos dados mostraram que o DHA a 100µM induziu a translocação de HMGB1 após 18 horas de estímulo e, em maior concentração, ela mostrou-se acumulada próxima à membrana celular de MDA-MB-231.…”