Sika deer antler protein against acetaminophen-induced oxidative stress and apoptosis in HK-2 cells via activating Nrf2/keap1/HO-1 pathway. 2019

Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
College of Chinese Medicine Materials, Jilin Agricultural University, Chang Chun, China.

Nf-E2-related transcription factor 2 (Nrf2) helps cells fight oxidative stress events in vivo and in vitro by promoting the expression of antioxidants and detoxification enzymes. The necessary factors regulating Nrf2 activity and stability during analgesic nephropathy are not fully understood. Our results suggest that acetaminophen produces nephrotoxicity in HK-2 cells by inhibiting keap1 degradation. APAP subsided Nrf2 nuclear accumulation by inhibition of keap1 degradation, thereby reducing the binding of Nrf2 to ARE, leading to the loss of expression of antioxidant proteins such as HO-1, inducing a series of oxidative stress and apoptosis events. Therefore, Nrf2/keap1/HO-1 signal transduction pathway has a poor prognosis during analgesic nephrotoxicity. Sika deer antler protein (SDAPR) significantly prevented APAP-induced HK-2 cell damage by constitutively stabilized Nrf2 nuclear retention. Excess APAP leads to a decrease in Nrf2 nuclear translocation, leading to severe oxidative stress, increasing the levels of GSH and MDA in HK-2 cells, and reducing the enzyme activities of SOD and CAT in HK-2 cells. Increased biomarker levels of acute kidney injury (AKI) in HK-2 cells, including kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and cystatin C, decrease the mitochondrial membrane potential in HK-2 cells, and cause mitochondrial dysfunction, it also reduced the ratio of mitochondria-associated apoptotic protein Bax/Bcl-2, leading to cell apoptosis. SDAPR dose dependently accorded protection against acetaminophen-induced nephrotoxicity, oxidative damage, and cell apoptosis by its molecular intervention with Nrf2/keap1/HO-1 pathway via keap1 degradation. PRACTICAL APPLICATIONS: In this paper, we investigated the protective effect of SDAPR on APAP-induced AKI in HK-2 cells, and briefly explained its possible mechanism of action, providing a basis for future clinical trials and the development of anti-APAP AKI drugs.

UI MeSH Term Description Entries
D003670 Deer The family Cervidae of 17 genera and 45 species occurring nearly throughout North America, South America, and Eurasia, on most associated continental islands, and in northern Africa. Wild populations of deer have been established through introduction by people in Cuba, New Guinea, Australia, New Zealand, and other places where the family does not naturally occur. They are slim, long-legged and best characterized by the presence of antlers. Their habitat is forests, swamps, brush country, deserts, and arctic tundra. They are usually good swimmers; some migrate seasonally. (Walker's Mammals of the World, 5th ed, p1362) Deers
D000071068 Lipocalin-2 A lipocalin of approximately 200 amino acids that functions as an iron transporter and is expressed by cells of BONE MARROW and many other cells with secretory functions. It is involved in APOPTOSIS and may function to limit pathogenic bacterial growth as part of the INNATE IMMUNE RESPONSE. Lipocalin-2 Protein,NGAL Protein,Neutrophil Gelatinase-Associated Lipocalin,Oncogene 24p3 Protein,Siderocalin Protein,Lipocalin 2,Lipocalin 2 Protein,Neutrophil Gelatinase Associated Lipocalin
D000072019 Kelch-Like ECH-Associated Protein 1 An adaptor protein characterized by an N-terminal BTB-POZ DOMAIN and six KELCH REPEATS that functions as a substrate for the E3 UBIQUITIN LIGASE complex. It negatively-regulates NF-E2-RELATED FACTOR 2 by targeting it for ubiquitination and degradation by the PROTEASOME. It also represses genes regulated by ANTIOXIDANT RESPONSE ELEMENTS. KEAP-1 Protein,KEAP1 Protein,KEAP 1 Protein,Kelch Like ECH Associated Protein 1
D000082 Acetaminophen Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000999 Antlers The horn of an animal of the deer family, typically present only in the male. It differs from the HORNS of other animals in being a solid, generally branched bony outgrowth that is shed and renewed annually. The word antler comes from the Latin anteocularis, ante (before) + oculus (eye). (From Webster, 3d ed) Antler
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

Related Publications

Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
October 2023, BMC nephrology,
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
September 2022, Antioxidants (Basel, Switzerland),
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
November 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
March 2021, Brain research bulletin,
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
May 2024, In vitro cellular & developmental biology. Animal,
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
January 2022, International heart journal,
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
November 2022, Current issues in molecular biology,
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
May 2022, Nan fang yi ke da xue xue bao = Journal of Southern Medical University,
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
June 2021, Experimental and therapeutic medicine,
Haonan Ruan, and Lulu Wang, and Jing Wang, and Hang Sun, and Xiaofeng He, and Wei Li, and Jing Zhang
January 2019, Oxidative medicine and cellular longevity,
Copied contents to your clipboard!