ArticleMedical science monitor : international medical journal of experimental and clinical research2018
Suppression of Apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs) by Klotho Protein is Associated with Reduced Endoplasmic Reticulum Oxidative Stress and Activation of the PI3K/AKT Pathway.
Article in Medical science monitor : international medical journal of experimental and clinical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Mechanisms of Cardiovascular Toxicity Induced by Silver Nanoparticles: A Systematic Review of Preclinical Evidence.Cardiovascular toxicology · 2026Pooled it
- α-Klotho Supplementation Mitigates Cumulative Exercise-Induced Fatigue via Coordinated NRF2-Mediated Antioxidant Defense and AKT/GS-Driven Hepatic Glycogen Supercompensation in Mice.International journal of molecular sciences · 2025Article
- Down-Regulation of Klotho/FGF23 by Low-Expressed VEGFR2 Inhibits the GH/IGF-1/PI3K/AKT Signaling Pathway Inducing Intrauterine Growth Restriction in Rats.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Article
- Klotho plasma levels are an independent predictorof mortality in women with acute coronary syndrome.Scientific reports · 2025Article
- The inflection point: α-Klotho levels and the risk of all-cause mortality.Frontiers in endocrinology · 2025Article
- Article
- The association between serum klotho protein and stroke: a cross-sectional study from NHANES 2007-2016.Frontiers in neurology · 2025Article
- Klotho relieves HInternational ophthalmology · 2024Article
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Hyaluronic acid restored protein permeability across injured human lung microvascular endothelial cells.FASEB bioAdvances · 2022Article
- Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway.Bioengineered · 2022Article
- Klotho alleviates chronic intermittent hypoxia-induced genioglossus myocyte apoptosis by inhibiting endoplasmic reticulum stress.Experimental and therapeutic medicine · 2021Article
- Klotho overexpression suppresses apoptosis by regulating the Hsp70/Akt/Bad pathway in H9c2(2-1) cells.Experimental and therapeutic medicine · 2021Article
- Silicon Oxynitrophosphide Nanoscale Coating Enhances Antioxidant Marker-Induced Angiogenesis During in vivo Cranial Bone-Defect Healing.JBMR plus · 2021Article
- Effects of Levistilide A on Hemorheology and Endothelial Cell Injury in Rats with Blood Stasis.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Gene expression of klotho & antioxidative enzymes in peripheral blood mononuclear cells of essential hypertension patients in Indian population.The Indian journal of medical research · 2020Article
- Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update.Journal of clinical medicine · 2020Review
- RecombinantAnalytical cellular pathology (Amsterdam) · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND Klotho protein has been shown to act as a hormone on the cardiovascular system, and to have specific protective effects on vascular endothelial cells. The aim of this study was to investigate the mechanisms of the anti-oxidative and anti-apoptotic effects of klotho protein on hydrogen peroxide (H₂O₂)-induced apoptosis and endoplasmic reticulum oxidative stress in human umbilical vein endothelial cells (HUVECs). MATERIAL AND METHODS HUVECs were cultured in vitro and treated with H₂O₂. The MTT assay evaluated cell viability of H₂O₂-treated HUVECs, and flow cytometry measured cell apoptosis. An enzyme-linked immunosorbent assay (ELISA) measured the levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6. Western blot was used to detect the expression of the proteins, 78 kD glucose-regulated protein (GRP78), CCAAT-enhancer-binding protein homologous protein (CHOP), caspase-3, caspase-9, caspase-12, and AKT. The effects of LY294002, a pharmacological inhibitor of PI3K, were evaluated. RESULTS Klotho protein increased the viability of H2O2-treated HUVECs and reduced the expression of NO, TNF-α, and IL-6. Klotho protein reduced the rate of apoptosis of H₂O₂-treated HUVECs and downregulated the expression of proteins associated with endoplasmic reticulum oxidative stress, GRP78 and CHOP, and the expression of the apoptotic proteins, caspase-3, caspase-9, and caspase-12, and activated the phosphorylation of AKT. The addition of LY294002 inhibited klotho protein downregulation of GRP78, CHOP, caspase-3, caspase-9, and caspase-12 expression. CONCLUSIONS In HUVECs, klotho protein suppressed apoptosis mediated by endoplasmic reticulum oxidative stress by activation of the PI3K/AKT pathway.
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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.