ArticleThe American journal of pathology2012
Pivotal role of apoptosis signal-regulating kinase 1 in monoclonal free light chain-mediated apoptosis.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 30 citations in OpenAlex.
- Noncrystalline light-chain proximal tubulopathy: a retrospective study from a single institute of China.Renal failure · 2026Article
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury.The Journal of clinical investigation · 2025Review
- Update on kidney injury caused by multiple myeloma.Annals of hematology · 2024Review
- Cellular antioxidant mechanisms control immunoglobulin light chain-mediated proximal tubule injury.Free radical biology & medicine · 2021Article
- The Proximal Tubule Toxicity of Immunoglobulin Light Chains.Kidney international reports · 2021Review
- Monoclonal glomerulopathy with features of cryoglobulinemic glomerulopathy in murine multiple myeloma model.Ultrastructural pathology · 2020Article
- Acute kidney injury in the patient with cancer.Kidney research and clinical practice · 2019Review
- Immunoglobulin light chains generate proinflammatory and profibrotic kidney injury.The Journal of clinical investigation · 2019Article
- Light Chain Cast Nephropathy: Practical Considerations in the Management of Myeloma Kidney-What We Know and What the Future May Hold.Current hematologic malignancy reports · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Renal failure, a major complication associated with multiple myeloma, is usually related to deposition of monoclonal immunoglobulin free light chains (FLCs) and directly contributes to morbidity and mortality in this disease. The present study focused on the cytotoxic effects of monoclonal FLCs. Human proximal tubular epithelial cells (HK-2) were examined after incubation with two human monoclonal FLCs (termed κ2 and λ3). Incubation of HK-2 cells for 24 and 48 hours with either FLCs at 1 mg/mL promoted activation of caspase-9 and caspase-3 and increased the rate of apoptosis. Because prior studies demonstrated that FLCs generated intracellular oxidative stress, our studies focused on the redox-sensitive mitogen-activated protein kinase kinase kinase known as apoptosis signal-regulating kinase 1 (ASK1). A time-dependent increase in phosphorylation of ASK1 at T845, indicating activation of this enzyme, was observed. Small interfering RNA designed to reduce ASK1 expression in HK-2 cells successfully decreased ASK1, which was confirmed by Western blot analysis. Incubation of ASK1-depleted HK-2 cells with the two FLCs prevented the increase in apoptosis while pretreating HK-2 cell with nontargeting small interfering RNA did not prevent FLCs-mediated apoptosis. The combined data demonstrate that monoclonal FLCs activated the intrinsic apoptotic pathway in renal epithelial cells by activation of ASK1.
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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.