The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach

Abstract

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.

Identification of potentially functional circRNAs and prediction of the circRNA-miRNA-hub gene network in mice with primary blast lung injury

“…For example, it has been reported that in hepatocellular carcinoma, the expression levels of CDK1 was positively correlated with the infiltration levels of CD4 + T cells, CD8 + T cells, neutrophils, macrophages and dendritic cells, suggesting that this gene may be involved in the recruitment and regulation of infiltrating cells in the immune microenvironment [ 33 ]. And in Bleomycin-induced ALI, the protein expression of Top2a was up-regulated, which leads to persistent inflammation and aggravation of alveolar epithelium [ 34 ]. Thus, these genes may be involved in immune regulation and inflammation balance in PBLI.…”

Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines

“…TGF-β1 protein levels were evaluated using Human TGF-β1 ELISA Kit (KRISHGEN biosystems, Mumbai, India). In addition, fibronectin and hydroxyproline were estimated by spectrophotometric and immunoassay techniques, as previously reported [116][117][118]. The absorbance (OD) of hydroxyproline in the supernatant of cancer cell lines was determined at wavelength 557 nm using a Systronics-2203 spectrophotometer (Systronics, Gujarat, India) [117].…”