Endotoxin Engages Mitochondrial Quality Control via an iNOS-Reactive Oxygen Species Signaling Pathway in Hepatocytes.
Anthony CyrLauran ChambersPaul K WaltzSean P WhelanLauryn KohutEvie CarchmanMitchell DyerJason LucianoBenjamin KautzaHernando D GomezLeo Edmond OtterbeinMatthew R RosengartSruti ShivaBrian S ZuckerbraunPublished in: Oxidative medicine and cellular longevity (2019)
LPS treatment inhibited aerobic respiration in vitro in wild-type but not iNos -/- cells. Experimental endotoxemia in vivo or in vitro induced iNOS protein and mtROS production. However, induction of mtROS was dependent on iNOS expression. Furthermore, LPS-induced hepatic autophagy/mitophagy and mitochondrial biogenesis were significantly attenuated in iNos -/- mice or cells with NO or mtROS scavenging. These responses were rescued in iNos -/- mice via delivery of NO both in vivo and in vitro. Conclusions. These data suggest that regulation of mitochondrial quality control following hepatocyte LPS exposure is dependent at least in part on a NO-mtROS signaling network. Further investigation to identify specific agents that modulate this process may facilitate the prevention of organ injury in sepsis.
Keyphrases
- quality control
- nitric oxide synthase
- induced apoptosis
- lps induced
- oxidative stress
- wild type
- inflammatory response
- signaling pathway
- cell cycle arrest
- endoplasmic reticulum stress
- reactive oxygen species
- nitric oxide
- cell death
- diabetic rats
- pi k akt
- high fat diet induced
- liver injury
- drug induced
- type diabetes
- high glucose
- cell proliferation
- small molecule
- long non coding rna
- replacement therapy
- data analysis