Caspase 1 Activation Is Protective against Hepatocyte Cell Death by Up-regulating Beclin 1 Protein and Mitochondrial Autophagy in the Setting of Redox Stress

Caspase 1 activation can be induced by oxidative stress, which leads to the release of the proinflammatory cytokines IL1β and IL18 in myeloid cells and a potentially damaging inflammatory response. However, little is known about the role of caspase 1 in non-immune cells, such as hepatocytes, that express and activate the inflammasome but do not produce a significant amount of IL1β/IL18. Here we demonstrate that caspase 1 activation protects against cell death after redox stress induced by hypoxia/reoxygenation in hepatocytes. Mechanistically, we show that caspase 1 reduces mitochondrial respiration and reactive oxygen species by increasing mitochondrial autophagy and subsequent clearance of mitochondria in hepatocytes after hypoxia/reoxygenation. Caspase 1 increases autophagic flux through up-regulating autophagy initiator beclin 1 during redox stress and is an important cell survival factor in hepatocytes. We find that during hemorrhagic shock with resuscitation, an in vivo mouse model associated with severe hepatic redox stress, caspase 1 activation is also protective against liver injury and excessive oxidative stress through the up-regulation of beclin 1. Our findings suggest an alternative role for caspase 1 activation in promoting adaptive responses to oxidative stress and, more specifically, in limiting reactive oxygen species production and damage in cells and tissues where IL1β/IL18 are not highly expressed.     

Resveratrol Protects against Cigarette Smoke–Induced Oxidative Damage and Pulmonary Inflammation

This study was carried out to investigate the effects of resveratrol on cigarette smoke (CS)–induced lung injury. Experimental mice were administrated with 1 mg/kg or 3 mg/ kg resveratrol orally, 1 h prior to CS exposure (five cigarettes a day for 3 consecutive days). Airway inflammation and gene expression changes were assessed. CS exposure increased the number of pulmonary inflammatory cells, coupled with elevated production of tumor necrosis factor α and interleukin‐6 in bronchoalveolar lavage fluids. Resveratrol treatment decreased CS‐induced lung inflammation. Resveratrol restored the activities of superoxide dismutase, GSH peroxidase, and catalase in CS‐treated mice. CS significantly enhanced the nuclear translocation of nuclear factor κB (NF‐κB) and NF‐κB DNA binding activity, which was impaired by resveratrol pretreatment. In addition, resveratrol promoted CS‐induced heme oxygenase‐1 (HO‐1) expression and activation. Our results collectively indicate that resveratrol attenuates CS‐induced lung oxidative injury, which involves decreased NF‐κB activity and the elevated HO‐1 expression and activity.