Dataset Information

Diindolylmethane Inhibits Cadmium-Induced Autophagic Cell Death via Regulation of Oxidative Stress in HEL299 Human Lung Fibroblasts.

ABSTRACT: Cadmium (Cd), a harmful heavy metal, can lead to various pulmonary diseases, including chronic obstructive pulmonary disease (COPD), by inducing cytotoxicity and disturbing redox homeostasis. The aim of the present study was to investigate Cd-mediated cytotoxicity using human lung fibroblasts and the therapeutic potential of 3,3'-diindolylmethane (DIM). Cadmium significantly reduced the cell viability of human embryonic lung (HEL299) cells accompanied by enhanced oxidative stress as evidenced by the increased expression of autophagy-related proteins such as LC3B and p62. However, treatment with DIM significantly suppressed autophagic cell death in Cd-induced HEL299 fibroblasts. In addition, DIM induced antioxidant enzyme activity and decreased intracellular reactive oxygen species (ROS) levels in Cd-damaged HEL299 cells. This study suggests that DIM effectively suppressed Cd-induced lung fibroblast cell death through the upregulation of antioxidant systems and represents a potential agent for the prevention of various diseases related to Cd exposure.

SUBMITTER: Jung YS

PROVIDER: S-EPMC9414701 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Diindolylmethane Inhibits Cadmium-Induced Autophagic Cell Death via Regulation of Oxidative Stress in HEL299 Human Lung Fibroblasts.

Jung Yeon-Seop YS Lee Ho Jeong HJ Hyun Moonjung M Kim Hye-Jin HJ Kim Je-Hein JH Hwang Kwang-Hyun KH Kim Woong-Soo WS Choi Jungil J Heo Jeong Doo JD

Molecules (Basel, Switzerland) 20220816 16

Cadmium (Cd), a harmful heavy metal, can lead to various pulmonary diseases, including chronic obstructive pulmonary disease (COPD), by inducing cytotoxicity and disturbing redox homeostasis. The aim of the present study was to investigate Cd-mediated cytotoxicity using human lung fibroblasts and the therapeutic potential of 3,3'-diindolylmethane (DIM). Cadmium significantly reduced the cell viability of human embryonic lung (HEL299) cells accompanied by enhanced oxidative stress as evidenced by ...[more]

PMID: 36014455

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Project description:Both environmental exposure to vanadium pentoxide (V2O5, V+5 for its ionic counterparts) and fibroblast senescence are associated with pulmonary fibrosis, but whether V+5 causes fibroblast senescence remains unknown. We found in a dose-response study that 2-40 μM V+5 caused human lung fibroblasts (HLF) senescence with increased senescence-associated β-galactosidase activity and p16 expression, while cell death occurred at higher concentration (LC50, 82 μM V+5). Notably, measures of reactive oxygen species (ROS) production with fluorescence probes showed no association of ROS with V+5-dependent senescence. Preloading catalase (polyethylene-conjugated), a H2O2 scavenger, did not alleviate the cellular senescence induced by V+5. Analyses of the cellular glutathione (GSH) system showed that V+5 oxidized GSH, increased GSH biosynthesis, stimulated cellular GSH efflux and increased protein S-glutathionylation, and addition of N-acetyl cysteine inhibited V+5-elevated p16 expression, suggesting that thiol oxidation mediates V+5-caused senescence. Moreover, strong correlations between GSSG/GSH redox potential (Eh), protein S-glutathionylation, and cellular senescence (R2 > 0.99, p < 0.05) were present in V+5-treated cells. Studies with cell-free and enzyme-free solutions showed that V+5 directly oxidized GSH with formation of V+4 and GSSG in the absence of O2. Analyses of V+5 and V+4 in HLF and culture media showed that V+5 was reduced to V+4 in cells and that a stable V+4/V+5 ratio was rapidly achieved in extracellular media, indicating ongoing release of V+4 and reoxidation to V+5. Together, the results show that V+5-dependent fibroblast senescence is associated with a cellular/extracellular redox cycling mechanism involving the GSH system and occurring under conditions that do not cause cell death. These results establish a mechanism by which environmental vanadium from food, dietary supplements or drinking water, can cause or contribute to lung fibrosis in the absence of high-level occupational exposures and cytotoxic cell death.

Dataset Information

Diindolylmethane Inhibits Cadmium-Induced Autophagic Cell Death via Regulation of Oxidative Stress in HEL299 Human Lung Fibroblasts.

Publications

Diindolylmethane Inhibits Cadmium-Induced Autophagic Cell Death via Regulation of Oxidative Stress in HEL299 Human Lung Fibroblasts.

Similar Datasets

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