Mitochondrial Respiratory Dysfunction Induces Claudin-1 Expression via Reactive Oxygen Species-mediated Heat Shock Factor 1 Activation, Leading to Hepatoma Cell Invasiveness

ABSTRACT Mpv17-like protein (M-LP) is a protein that has been suggested to be involved in the metabolism of reactive oxygen species. The two M-LP isoforms in mouse, M-LPS and M-LPL, are generated by the alternative usage of promoters. M-LPS is expressed exclusively in kidneys after the age of 6 weeks, whereas M-LPL is expressed ubiquitously. To elucidate the molecular basis of M-LPS expression, we searched for cis-regulatory elements in the promoter region of M-LPS and identified heat shock element half-sites as positive elements and a Tramtrack 69K (Ttk 69K) binding site as a negative element. Furthermore, we isolated a novel transcription repressor, Rhit (regulator of heat-induced transcription), that binds to the Ttk 69K binding site within the M-LPS promoter by DNA affinity chromatography and confirmed its participation in the transcriptional regulation of M-LPS by RNA interference (RNAi). Sequence analysis revealed that Rhit contains a KRAB (Krüppel-associated box) domain and a DNA-binding domain composed of eight C2H2-type zinc fingers. Interestingly, exposure to heat shock stress resulted in the upregulation of M-LPS expression concurrent with the downregulation of Rhit expression. Moreover, the age-dependent expression of M-LPS was inversely correlated with that of Rhit. These observations strongly suggest that Rhit acts as a repressor in the heat-induced and age-dependent transcriptional regulation of M-LPS.

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Heat Shock Protein 75 (TRAP1) Antagonizes Reactive Oxygen Species Generation and Protects Cells from Granzyme M-mediated Apoptosis

Journal of Biological Chemistry ◽

10.1074/jbc.m703196200 ◽

2007 ◽

Vol 282 (28) ◽

pp. 20553-20560 ◽

Cited By ~ 133

Author(s):

Guoqiang Hua ◽

Qixiang Zhang ◽

Zusen Fan

Keyword(s):

Reactive Oxygen Species ◽

Heat Shock ◽

Heat Shock Protein ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species

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Reactive Oxygen Species Interact With NLRP3 Inflammasomes and Are Involved in the Inflammation of Sepsis: From Mechanism to Treatment of Progression

Frontiers in Physiology ◽

10.3389/fphys.2020.571810 ◽

2020 ◽

Vol 11 ◽

Author(s):

Shuai Zhao ◽

Fan Chen ◽

Qiliang Yin ◽

Dunwei Wang ◽

Wei Han ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Inflammasome Activation ◽

Oxygen Species ◽

Negative Effects ◽

Respiratory Dysfunction ◽

Pyrin Domain ◽

Nlrp3 Inflammasome Activation ◽

Nlrp3 Inflammasomes ◽

Related Mortality

Over the past 10 years, the crisis of sepsis has remained a great challenge. According to data from 2016, the sepsis-related mortality rate remains high. In addition, sepsis consumes extensive medical resources in intensive care units, and anti-inflammatory agents fail to improve sepsis-associated hyperinflammation and symptoms of immunosuppression. The specific immune mechanism of sepsis remains to be elucidated. Reactive oxygen species (ROS) are triggered by energy metabolism and respiratory dysfunction in sepsis, which not only cause oxidative damage to tissues and organelles, but also directly and indirectly promote NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. NLRP3 inflammasomes enlarge the inflammatory response and trigger apoptosis of immune cells to exacerbate sepsis progression. Inhibiting the negative effects of ROS and NLRP3 inflammasomes therefore provides the possibility of reversing the excessive inflammation during sepsis. In this review, we describe the interaction of ROS and NLRP3 inflammasomes during sepsis, provide prevention strategies, and identify fields that need further study.

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