ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014
Inducible HSP70 regulates superoxide dismutase-2 and mitochondrial oxidative stress in the endothelial cells from developing lungs.
Article in American journal of physiology. Lung cellular and molecular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- Manipulation of HSP70-SOD1 Expression Modulates SH-SY5Y Differentiation and Susceptibility to Oxidative Stress-Dependent Cell Damage: Involvement in Oxotremorine-M-Mediated Neuroprotective Effects.Antioxidants (Basel, Switzerland) · 2023Article
- Hsp70 in Redox Homeostasis.Cells · 2022Review
- Genes and Longevity of Lifespan.International journal of molecular sciences · 2022Review
- Hif-1α/Hsf1/Hsp70 signaling pathway regulates redox homeostasis and apoptosis in large yellow croaker (Zoological research · 2021Article
- Decreased Cyclic Guanosine Monophosphate-Protein Kinase G Signaling Impairs Angiogenesis in a Lamb Model of Persistent Pulmonary Hypertension of the Newborn.American journal of respiratory cell and molecular biology · 2021Article
- Modulation of the Nitric Oxide/BH4 Pathway Protects Against Irradiation-Induced Neuronal Damage.Neurochemical research · 2021Article
- Response to oxidative stress of peripheral blood mononuclear cells from multiple sclerosis patients and healthy controls.Cell stress & chaperones · 2020Article
- Decreased OLA1 (Obg-Like ATPase-1) Expression Drives Ubiquitin-Proteasome Pathways to Downregulate Mitochondrial SOD2 (Superoxide Dismutase) in Persistent Pulmonary Hypertension of the Newborn.Hypertension (Dallas, Tex. : 1979) · 2019Article
- The Complex Phosphorylation Patterns that Regulate the Activity of Hsp70 and Its Cochaperones.International journal of molecular sciences · 2019Review
- Effects of exercise preconditioning and HSP72 on diaphragm muscle function during mechanical ventilation.Journal of cachexia, sarcopenia and muscle · 2019Article
- Gene expression analysis of heat-shock proteins and redox regulators reveals combinatorial prognostic markers in carcinomas of the gastrointestinal tract.Redox biology · 2019Article
- KU-596 decreases mitochondrial superoxide and improves bioenergetics following downregulation of manganese superoxide dismutase in diabetic sensory neurons.Experimental neurology · 2019Article
- A longitudinal study of neurotrophic, oxidative, and inflammatory markers in first-onset depression in midlife women.European archives of psychiatry and clinical neuroscience · 2018Article
- Dynamic Phosphorylation of the C Terminus of Hsp70 Regulates the Mitochondrial Import of SOD2 and Redox Balance.Cell reports · 2018Article
- Persistent pulmonary hypertension alters the epigenetic characteristics of endothelial nitric oxide synthase gene in pulmonary artery endothelial cells in a fetal lamb model.Physiological genomics · 2018Article
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Zinc Oxide Nanoparticles Induced Oxidative DNA Damage, Inflammation and Apoptosis in Rat's Brain after Oral Exposure.Toxics · 2018Article
- Mitochondrial dysfunction and pulmonary hypertension: cause, effect, or both.American journal of physiology. Lung cellular and molecular physiology · 2018Review
- CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2.Immunity & ageing : I & A · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Superoxide dismutase 2 (SOD-2) is synthesized in the cytosol and imported into the mitochondrial matrix, where it is activated and functions as the primary antioxidant for cellular respiration. The specific mechanisms that target SOD-2 to the mitochondria remain unclear. We hypothesize that inducible heat shock protein 70 (iHSP70) targets SOD-2 to the mitochondria via a mechanism facilitated by ATP, and this process is impaired in persistent pulmonary hypertension of the newborn (PPHN). We observed that iHSP70 interacts with SOD-2 and targets SOD-2 to the mitochondria. Interruption of iHSP70-SOD-2 interaction with 2-phenylethylenesulfonamide-μ (PFT-μ, a specific inhibitor of substrate binding to iHSP70 COOH terminus) and siRNA-mediated knockdown of iHSP70 expression disrupted SOD-2 transport to mitochondria. Increasing intracellular ATP levels by stimulation of respiration with CaCl2 facilitated the mitochondrial import of SOD-2, increased SOD-2 activity, and decreased the mitochondrial superoxide (O2(·-)) levels in PPHN pulmonary artery endothelial cells (PAEC) by promoting iHSP70-SOD-2 dissociation at the outer mitochondrial membrane. In contrast, oligomycin, an inhibitor of mitochondrial ATPase, decreased SOD-2 expression and activity and increased O2(·-) levels in the mitochondria of control PAEC. The basal ATP levels and degree of iHSP70-SOD-2 dissociation were lower in PPHN PAEC and lead to increased SOD-2 degradation in cytosol. In normal pulmonary arteries (PA), PFT-μ impaired the relaxation response of PA rings in response to nitric oxide (NO) donor, S-nitroso-N-acetyl-penicillamine. Pretreatment with Mito-Q, a mitochondrial targeted O2(·-) scavenger, restored the relaxation response in PA rings pretreated with PFT-μ. Our observations suggest that iHSP70 chaperones SOD-2 to the mitochondria. Impaired SOD-2-iHSP70 dissociation decreases SOD-2 import and contributes to mitochondrial oxidative stress in PPHN.
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