ArticlePediatric research2016
Simvastatin attenuates oleic acid-induced oxidative stress through CREB-dependent induction of heme oxygenase-1 in renal proximal tubule cells.
Article in Pediatric research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Adenosine/AmBio · 2026Article
- Statins as Modulators of Epithelial to Mesenchymal Transition in Cardiovascular-Kidney-Metabolic Syndrome: a Comprehensive Review of Mechanisms and Therapeutic Implications.Current atherosclerosis reports · 2025Review
- Antioxidant Effects of Statins by Modulating Nrf2 and Nrf2/HO-1 Signaling in Different Diseases.Journal of clinical medicine · 2022Review
- Nimodipine promotes neurite outgrowth and protects against neurotoxicity in PC12 cells.Iranian journal of basic medical sciences · 2021Article
- The Novel Neuroprotective Compound KMS99220 Has an Early Anti-neuroinflammatory Effect via AMPK and HO-1, Independent of Nrf2.Experimental neurobiology · 2018Article
- Curcumin attenuates hypoxic-ischemic brain injury in neonatal rats through induction of nuclear factor erythroid-2-related factor 2 and heme oxygenase-1.Experimental and therapeutic medicine · 2017Article
- Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials.Current hypertension reviews · 2017Article
- Chronic Nicotine Exposure Reduces Antioxidant Function of Simvastatin in Renal Proximal Tubule Cells.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStatins elicit antioxidant effects independently of their lipid-lowering properties. Heme oxygenase-1 (HO-1) induction may be a part of these pleiotropic effects, which are insufficiently described in the kidney. We hypothesize that simvastatin (SIM) transcriptionally activates HO-1 that protects renal proximal tubule cells from lipotoxic injury.
methodsImpact of SIM on 100 μmol/l oleic acid (OA)-mediated reactive oxygen species (ROS) production and consequent oxidative stress (4-hydroxynonenal (HNE) content) as well as cell injury/apoptosis (lactate dehydrogenase (LDH) release, caspase-3 activation) were determined in cultured renal proximal tubule (NRK52E) cells. Effect of SIM on the HO-1 promoter and its enhancer elements (antioxidant response element (ARE), CCAAT, AP1, and cAMP response element (CRE)) was also determined in reporter luciferase assays. Dominant-negative (dnMEK, M1CREB) and pharmacologic (H89) approaches were used to inhibit activation of extracellular signal regulated kinase (ERK), CREB, and protein kinase A (PKA), respectively.
resultsSIM dose-dependently activated the HO-1 promoter that was essential for protection against OA-dependent ROS production/oxidative stress and LDH release/caspase-3 activation. We found that the HO-1 promoter was induced through ERK and PKA-dependent activation of the CRE by SIM.
conclusionSIM may protect the kidney from adverse effects of circulating fatty acids by upregulating the antioxidant HO-1, aside from its well-described lipid-lowering effects.
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