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- Title
Rotenone-Induced 4-HNE Aggresome Formation and Degradation in HL-1 Cardiomyocytes: Role of Autophagy Flux.
- Authors
Sharma, Sudha; Patel, Foram; Ara, Hosne; Bess, Ezra; Shum, Alika; Bhattarai, Susmita; Subedi, Utsab; Bell, Daquonte Sanard; Bhuiyan, Md. Shenuarin; Sun, Hong; Batinic-Haberle, Ines; Panchatcharam, Manikandan; Miriyala, Sumitra
- Abstract
Reactive oxygen species (ROS) cause oxidative stress by generating reactive aldehydes known as 4-hydroxynonenal (4-HNE). 4-HNE modifies protein via covalent adduction; however, little is known about the degradation mechanism of 4-HNE-adducted proteins. Autophagy is a dynamic process that maintains cellular homeostasis by removing damaged organelles and proteins. In this study, we determined the role of a superoxide dismutase (SOD) mimetic MnTnBuOE-2-PyP5+ (MnP, BMX-001) on rotenone-induced 4-HNE aggresome degradation in HL-1 cardiomyocytes. A rotenone treatment (500 nM) given for 24 h demonstrated both increased ROS and 4-HNE aggresome accumulation in HL-1 cardiomyocytes. In addition, cardiomyocytes treated with rotenone displayed an increase in the autophagy marker LC3-II, as shown by immunoblotting and immunofluorescence. A pre-treatment with MnP (20 µM) for 24 h attenuated rotenone-induced ROS formation. An MnP pre-treatment showed decreased 4-HNE aggresomes and LC3-II formation. A rotenone-induced increase in autophagosomes was attenuated by a pre-treatment with MnP, as shown by fluorescent-tagged LC3 (tfLC3). Rotenone increased tubulin hyperacetylation through the ROS-mediated pathway, which was attenuated by MnP. The disruption of autophagy caused HL-1 cell death because a 3-methyladenine inhibitor of autophagosomes caused reduced cell death. Yet, rapamycin, an inducer of autophagy, increased cell death. These results indicated that a pre-treatment with MnP decreased rotenone-induced 4-HNE aggresomes by enhancing the degradation process.
- Subjects
ADDUCTION; AUTOPHAGY; REACTIVE oxygen species; ROTENONE; SUPEROXIDE dismutase; CELL death
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 9, p4675
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23094675