ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2010
CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 185 citations in OpenAlex.
- Changes of the Fatty Acid Profile in Erythrocyte Membranes of Patients following 6-Month Dietary Intervention Aimed at the Regression of Nonalcoholic Fatty Liver Disease (NAFLD).Canadian journal of gastroenterology & hepatology · 2018Trial
- The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans.The Journal of clinical investigation · 2012Trial
- CerS2-mediated lipotoxicity and calcium signaling: a novel sequential mechanism of apoptosis in cancer.The Biochemical journal · 2026Review
- Ophiobolin A Induces an Apoptotic Transcriptional Signature and Modulates Redox Homeostasis in T98G and U118MG Glioblastoma Cells: A Machine Learning Approach.International journal of molecular sciences · 2026Article
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer.Pharmacological reviews · 2025Review
- ER Stress Induced by Artemisinin and Its Derivatives Determines the Susceptibility to Their Synergistic Apoptotic Killing With TRAIL.Cancer medicine · 2025Article
- The PERK-eIF2α-ATF4 Axis Is Involved in Mediating ER-Stress-Induced Ferroptosis via DDIT4-mTORC1 Inhibition and Acetaminophen-Induced Hepatotoxicity.Antioxidants (Basel, Switzerland) · 2025Article
- MASH as an emerging cause of hepatocellular carcinoma: current knowledge and future perspectives.Molecular oncology · 2025Review
- Updated mechanisms of MASLD pathogenesis.Lipids in health and disease · 2024Review
- Hepatocyte programmed cell death: the trigger for inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis.Frontiers in cell and developmental biology · 2024Review
- Cell-type specific role of autophagy in the liver and its implications in non-alcoholic fatty liver disease.World journal of hepatology · 2023Article
- The Role of Endoplasmic Reticulum in Lipotoxicity during Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Pathogenesis.The American journal of pathology · 2023Review
- The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging.Nature communications · 2023Article
- Association of post-smoking cessation changes in fasting serum glucose with changes in predicted fatty liver score.Scientific reports · 2023Article
- Review
- EVA1A regulates hematopoietic stem cell regeneration via ER-mitochondria mediated apoptosis.Cell death & disease · 2023Article
- Moutan Cortex Extract Modulates Macrophage Activation via Lipopolysaccharide-Induced Calcium Signaling and ER Stress-CHOP Pathway.International journal of molecular sciences · 2023Article
- PNPLA3 148M/M Is More Susceptible to Palmitic Acid-Induced Endoplasmic Reticulum Stress-Associated Apoptosis in HepG2 Cells.International journal of endocrinology · 2023Article
- Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK.Biomedicines · 2022Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress-mediated apoptosis is a key feature of hepatocyte cytotoxicity by saturated free fatty acids (FFA). This lipoapoptosis is dependent, in part, on the transcriptional upregulation of the BH3-only protein PUMA (p53 upregulated modulator of apoptosis). Although the activator protein (AP)-1 complex facilitates PUMA expression by saturated FFA, the transcription factor CAAT/enhancer binding homologous protein (CHOP) is also induced by ER stress and promotes apoptosis. To integrate the role of these two transcription factors in ER stress-induced apoptosis, we examined the relative contribution of CHOP and AP-1 in mediating PUMA induction by saturated FFA. Our results demonstrate that short-hairpin RNA-targeted knockdown of CHOP attenuates palmitate-induced apoptosis in Huh-7 cells. Loss of CHOP induction also reduced the increase in PUMA mRNA and protein levels as well as Bax activation by palmitate. No functional CHOP binding sites were identified in the PUMA promoter sequence. Rather, we observed that CHOP physically interacts with the AP-1 complex protein c-Jun upon palmitate treatment, and a CHOP:phosphorylated c-Jun heteromeric complex binds to the AP-1 consensus binding sequence within the PUMA promoter region. Finally, loss of function studies suggest that both transcription factors are necessary for maximal PUMA induction. Collectively, these data suggest that CHOP and AP-1 cooperatively mediate PUMA induction during hepatocyte lipoapoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.