Andrographolide-induced apoptosis in human renal tubular epithelial cells: Roles of endoplasmic reticulum stress and inflammatory response

Gu, Leyi; Zhang, Xinyue; Xing, Wenmin; Xu, Jing; Hong, Lü

doi:10.1016/j.etap.2016.02.004

Cited by 30 publications

(15 citation statements)

References 37 publications

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“…TNFα can be secreted from cells to induce an inflammatory response as a protective mechanism during initial exposure to toxicants [28]. TNFα expression can induce reactive oxygen species generation via mitochondria and through activation of NADPH oxidase [29].…”

Section: Discussionmentioning

confidence: 99%

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

Murphy

Stafford

Petrasovits

et al. 2017

IJMS

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Tenofovir (TFV) is an antiviral drug approved for treating Human Immunodeficiency Virus (HIV) and Hepatitis B. TFV is administered orally as the prodrug tenofovir disoproxil fumarate (TDF) which then is deesterified to the active drug TFV. TFV induces nephrotoxicity characterized by renal failure and Fanconi Syndrome. The mechanism of this toxicity remains unknown due to limited experimental models. This study investigated the cellular mechanism of cytotoxicity using a human renal proximal tubular epithelial cell line (HK-2). HK-2 cells were grown for 48 h followed by 24 to 72 h exposure to 0–28.8 μM TFV or vehicle, phosphate buffered saline (PBS). MTT (MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and Trypan blue indicated that TFV diminished cell viability at 24–72 h. TFV decreased ATP levels at 72 h when compared to vehicle, reflecting mitochondrial dysfunction. TFV increased the oxidative stress biomarkers of protein carbonylation and 4-hydroxynonenol (4-HNE) adduct formation. Tumor necrosis factor alpha (TNFα) was released into the media following exposure to 14.5 and 28.8 μM TFV. Caspase 3 and 9 cleavage was induced by TFV compared to vehicle at 72 h. These studies show that HK-2 cells are a sensitive model for TFV cytotoxicity and suggest that mitochondrial stress and apoptosis occur in HK-2 cells treated with TFV.

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Section: Discussionmentioning

confidence: 99%

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

Murphy

Stafford

Petrasovits

et al. 2017

IJMS

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“…Various causes lead to misfolding of proteins in the ER, and the accumulation of misfolded proteins in the lumen and the imbalance of Ca 2+ , which is called ER stress. Persistent and severe ER stress can induce apoptosis, and the pathogenesis of many diseases is related to the apoptosis caused by ER stress . A series of cellular responses to reduce ER stress are known as unfolded protein responses (UPRs), including pathways activated by three transcription factors (IRE1, ATF6, and PERK) .…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, cells were seeded into a 96-well plate at a density of 5 × 10 4 cells/mL, and divided into blank control, normal control and Ost group. Medium containing 50, 100, 150, 200, 250, and 300 μmol/L of Ost was added into each well in a volume of 100 μL and at different time points (12,24, and 48 hours), respectively. Four replicated wells were set up for each group.…”

Section: Mtt Assaymentioning

confidence: 99%

“…Persistent and severe ER stress can induce apoptosis, and the pathogenesis of many diseases is related to the apoptosis caused by ER stress. 24 A series of cellular responses to reduce ER stress are known as unfolded protein responses (UPRs), including pathways activated by three transcription factors (IRE1, ATF6, and PERK). 25 Under normal conditions, they are attached to the ER molecule chaperone GRP78 and are in a resting state.…”

Section: Effect Of Ost On Er Stress Associated Protein Expression Imentioning

confidence: 99%

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Osthole induced apoptosis in human normal liver cells by regulating cell proliferation and endoplasmic reticulum stress

Shen

Chen

Hong

2019

Environmental Toxicology

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Osthole (Ost) is often used in treatment for cancer, inflammation and rheumatism in clinic. However, Ost‐induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of Ost‐induced hepatotoxicity in human normal liver cells (L02). When cells were exposed to Ost, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, Ost altered apoptotic related proteins levels, including Bcl‐2, Bax, Cleaved‐Caspase‐9/‐8/‐3, and Pro‐Caspase‐3/‐8. In addition, Ost enhanced the levels of endoplasmic reticulum (ER) stress proteins (GRP78/Bip, CHOP, Caspase‐4, IRE1α, PERK, JNK, P‐JNK, and ATF4), decreased the cell proliferation and cycle‐associated protein (Phospho‐Histone H3, P‐Cdc25C, Cdc25C, P‐Cdc2, Cdc2, and Cyclin B1) level. The results show that Ost has toxic effects on L02 cells. Furthermore, it induces apoptosis by inhibiting cell proliferation, arresting cell cycle at the G2/M phase and activating ER stress.

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“…SOD, CAT, and GSH activities decreased in the gastric tissue of rats treated with indomethacin. Oral administration of andrographolide sodium bisulfate (40,80, and 160 mg/kg) 7 days before treatment with indomethacin reduced oxidative stress by restoring SOD, CAT, and GSH activities [72]. Mice treated with arsenic have decreased SOD and CAT activities.…”

Section: In Vivo Studiesmentioning

confidence: 99%

Andrographolide, A Natural Antioxidant: An Update

et al. 2019

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Traditionally, Andrographis paniculata has been used as an herbal remedy for lung infection treatments. Its leaves contain a diterpenoid labdane called andrographolide responsible for a wide range of biological activities such as antioxidant, anti-inflammatory, and anti-cancer properties. This manuscript is a brief review of the antioxidant mechanisms and the regulation of the Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling pathway by andrographolide.

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Andrographolide-induced apoptosis in human renal tubular epithelial cells: Roles of endoplasmic reticulum stress and inflammatory response

Cited by 30 publications

References 37 publications

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

Osthole induced apoptosis in human normal liver cells by regulating cell proliferation and endoplasmic reticulum stress

Andrographolide, A Natural Antioxidant: An Update

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