The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach.
Sadiya Bi ShaikhMohd Altaf NajarAshwini PrabhuD A B RexJaikanth ChanderasekaranSantosh Kumar BeheraPrashant Kumar ModiThottethodi Subrahmanya Keshava PrasadYashodhar Prabhakar BhandaryPublished in: BioFactors (Oxford, England) (2021)
Bleomycin (BLM) injury is associated with the severity of acute lung injury (ALI) leading to fibrosis, a high-morbidity, and high-mortality respiratory disease of unknown etiology. BLM-induced ALI is marked by the activation of a potent fibrogenic cytokine transcription growth factor beta-1 (TGFβ-1), which is considered a critical cytokine in the progression of alveolar injury. Previously, our work demonstrated that a diet-derived compound curcumin (diferuloylmethane), represents its antioxidative and antifibrotic application in TGF-β1-mediated BLM-induced alveolar basal epithelial cells. However, curcumin-specific protein targets, as well as its mechanism using mass spectrometry-based proteomic approach, remain elusive. To elucidate the underlying mechanism, a quantitative proteomics approach and bioinformatics analysis were employed to identify the protein targets of curcumin in BLM or TGF-β1-treated cells. With subsequent in vitro experiments, curcumin-related pathways and cellular processes were predicted and validated. The current study discusses two separate proteomics experiments using BLM and TGF-β1-treated cells with the proteomics approach, various unique target proteins were identified, and proteomic analysis revealed that curcumin reversed the expressions of unique proteins like DNA topoisomerase 2-alpha (TOP2A), kinesin-like protein (KIF11), centromere protein F (CENPF), and so on BLM or TGF-β1 injury. For the first time, the current study reveals that curcumin restores TGF-β1 induced peroxisomes like PEX-13, PEX-14, PEX-19, and ACOX1. This was verified by subsequent in vitro assays. This study generated molecular evidence to deepen our understanding of the therapeutic role of curcumin at the proteomic level and may be useful to identify molecular targets for future drug discovery.
Keyphrases
- mass spectrometry
- transforming growth factor
- growth factor
- induced apoptosis
- high glucose
- drug discovery
- diabetic rats
- label free
- lipopolysaccharide induced
- oxidative stress
- high resolution
- protein protein
- type diabetes
- single molecule
- lps induced
- inflammatory response
- anti inflammatory
- endothelial cells
- small molecule
- physical activity
- weight loss
- coronary artery disease
- liquid chromatography
- cardiovascular events
- cell death
- ms ms