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  1. Article ; Online: Cell death induced by acute kidney injury: A perspective on the contributions of accidental and programmed cell death.

    Noh, Mi Ra / Padanilam, Babu J

    American journal of physiology. Renal physiology

    2024  

    Abstract: The involvement of cell death in AKI is linked to multiple factors including nucleotide depletion, electrolyte imbalance, reactive oxygen species, endonucleases, disturbance of mitochondrial integrity, and activation of several cell death pathway ... ...

    Abstract The involvement of cell death in AKI is linked to multiple factors including nucleotide depletion, electrolyte imbalance, reactive oxygen species, endonucleases, disturbance of mitochondrial integrity, and activation of several cell death pathway components. Since our review in 2003, discussing the relative contributions of apoptosis and necrosis, several other forms of cell death have been identified and are shown to contribute to acute kidney injury (AKI). Currently, these various forms of cell death can be fundamentally divided into accidental cell death (ACD) and regulated or programmed cell death (RCD/PCD) based on functional aspects. Several death initiator and effector molecules, switch molecules that may act as signaling components triggering either death or protective mechanisms or alternate cell death pathways have been identified as part of the machinery. Intriguingly, several of these cell death pathways share components and signaling pathways suggesting complementary or compensatory functions. Thus defining the crosstalk between distinct cell death pathways and identifying the unique molecular effectors for each type of cell death may be required to develop novel strategies to prevent cell death. Further, depending on the multiple forms of cell death simultaneously induced in different AKI settings, strategies for combination therapies that block multiple cell death pathways need to be developed to completely prevent injury, cell death and renal function. This review highlights the various cell death pathways, crosstalk and interactions between different cell death modalities in AKI.
    Language English
    Publishing date 2024-04-25
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00275.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Presence of Testis Determines Aristolochic Acid-Induced Nephrotoxicity in Mice.

    Li, Wei-Long / Padanilam, Babu J / Kim, Jinu

    Toxins

    2023  Volume 15, Issue 2

    Abstract: Aristolochic acid (AA) is notorious for inducing nephrotoxicity, but the influence of sex on AA-induced kidney injury was not clear. This study sought to investigate sex differences in kidney dysfunction and tubular injury induced by AA. Male and female ... ...

    Abstract Aristolochic acid (AA) is notorious for inducing nephrotoxicity, but the influence of sex on AA-induced kidney injury was not clear. This study sought to investigate sex differences in kidney dysfunction and tubular injury induced by AA. Male and female mice were bilaterally orchiectomized and ovariectomized, respectively. Fourteen days after gonadectomy, the mice were intraperitoneally injected with AA (10 mg/kg body weight/day) daily for 2 days and sacrificed 7 days after the first injection. Body weight, kidney function, and tubular structure were assessed. When compared between male and female non-gonadectomized mice, AA-induced body weight loss was greater in male mice than in female mice. Functional and structural damages in male kidneys were markedly induced by AA injection, but kidneys in AA-injected female mice showed no or mild damages. Ovariectomy had no effect on AA-induced nephrotoxic acute kidney injury in female mice. However, orchiectomy significantly reduced body weight loss, kidney dysfunction, and tubular injury in AA-induced nephrotoxicity in male mice. This study has demonstrated that testis causes AA-induced nephrotoxic acute kidney injury.
    MeSH term(s) Mice ; Female ; Male ; Animals ; Testis ; Kidney ; Aristolochic Acids/toxicity ; Acute Kidney Injury/chemically induced ; Body Weight ; Weight Loss
    Chemical Substances aristolochic acid I (94218WFP5T) ; Aristolochic Acids
    Language English
    Publishing date 2023-02-01
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins15020118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Epoxyeicosatrienoic acid activation moderates endothelial mesenchymal transition to reduce obstructive nephropathy.

    Padanilam, Babu J

    Kidney research and clinical practice

    2017  Volume 36, Issue 4, Page(s) 299–301

    Language English
    Publishing date 2017-12-31
    Publishing country Korea (South)
    Document type Editorial
    ZDB-ID 2656420-8
    ISSN 2211-9132
    ISSN 2211-9132
    DOI 10.23876/j.krcp.2017.36.4.299
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Repeated Administration of Cisplatin Transforms Kidney Fibroblasts through G2/M Arrest and Cellular Senescence.

    Yu, Jia-Bin / Lee, Dong-Sun / Padanilam, Babu J / Kim, Jinu

    Cells

    2022  Volume 11, Issue 21

    Abstract: Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer, but it has nephrotoxic side effects leading to acute kidney injury and subsequently chronic kidney disease (CKD). Previous work has focused on acute kidney tubular ... ...

    Abstract Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer, but it has nephrotoxic side effects leading to acute kidney injury and subsequently chronic kidney disease (CKD). Previous work has focused on acute kidney tubular injury induced by cisplatin, whereas the chronic sequelae post-injury has not been well-explored. In the present study, we established a kidney fibroblast model of CKD induced by repeated administration of cisplatin (RAC) as a clinically relevant model. In NRK-49F rat kidney fibroblasts, RAC upregulated α-smooth muscle actin (α-SMA) and fibronectin proteins, suggesting that RAC induces kidney fibroblast-to-myofibroblast transformation. RAC also enhanced cell size, including the cell attachment surface area, nuclear area, and cell volume. Furthermore, RAC induced p21 expression and senescence-associated β-galactosidase activity, suggesting that kidney fibroblasts exposed to RAC develop a senescent phenotype. Inhibition of p21 reduced cellular senescence, hypertrophy, and myofibroblast transformation induced by RAC. Intriguingly, after RAC, kidney fibroblasts were arrested at the G2/M phase. Repeated treatment with paclitaxel as an inducer of G2/M arrest upregulated p21, α-SMA, and fibronectin in the kidney fibroblasts. Taken together, these data suggest that RAC transforms kidney fibroblasts into myofibroblasts through G2/M arrest and cellular senescence.
    MeSH term(s) Rats ; Animals ; Cisplatin/pharmacology ; Cisplatin/metabolism ; Fibronectins/metabolism ; Apoptosis ; Cell Line, Tumor ; G2 Phase Cell Cycle Checkpoints ; Cellular Senescence ; Fibroblasts/metabolism ; Kidney/metabolism ; Renal Insufficiency, Chronic/metabolism
    Chemical Substances Cisplatin (Q20Q21Q62J) ; Fibronectins
    Language English
    Publishing date 2022-11-02
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11213472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: 2-Mercaptoethanol protects against DNA double-strand breaks after kidney ischemia and reperfusion injury through GPX4 upregulation.

    Moon, Daeun / Padanilam, Babu J / Jang, Hee-Seong / Kim, Jinu

    Pharmacological reports : PR

    2022  Volume 74, Issue 5, Page(s) 1041–1053

    Abstract: Background: Kidney ischemia reperfusion injury (IRI) is characterized by tubular cell death. DNA double-strand breaks is one of the major sources of tubular cell death induced by IRI. 2-Mercaptoethanol (2-ME) is protective against DNA double-strand ... ...

    Abstract Background: Kidney ischemia reperfusion injury (IRI) is characterized by tubular cell death. DNA double-strand breaks is one of the major sources of tubular cell death induced by IRI. 2-Mercaptoethanol (2-ME) is protective against DNA double-strand breaks derived from calf thymus and bovine embryo. Here, we sought to determine whether treatment with 2-ME attenuated DNA double-strand breaks, resulting in reduced kidney dysfunction and structural damage in IRI.
    Methods: Kidney IRI or sham-operation in mice was carried out. The mice were treated with 2-ME, Ras-selective lethal 3, or vehicle. Kidney function, tubular injury, DNA damage, antioxidant enzyme expression, and DNA damage response (DDR) kinases activation were assessed.
    Results: Treatment with 2-ME significantly attenuated kidney dysfunction, tubular injury, and DNA double-strand breaks after IRI. Among DDR kinases, IRI induced phosphorylation of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR), but IRI reduced phosphorylation of other DDR kinases including ataxia telangiectasia and Rad3 related, checkpoint kinase 1 (Chk1), Chk2, and Chinese hamster cells 1 (XRCC1). Treatment with 2-ME enhanced phosphorylation of ATM and ATM-mediated effector kinases in IRI-subjected kidneys, suggesting that 2-ME activates ATM-mediated DDR signaling pathway. Furthermore, 2-ME dramatically upregulated glutathione peroxidase 4 (GPX4) in IRI-subjected kidneys. Inhibition of GPX4 augmented adverse IRI consequences including kidney dysfunction, tubular injury, DNA double-strand breaks, and inactivation of ATM-mediated DDR signaling pathway after IRI in 2-ME-treated kidneys.
    Conclusions: We have demonstrated that exogenous 2-ME protects against DNA double-strand breaks after kidney IRI through GPX4 upregulation and ATM activation.
    MeSH term(s) Cattle ; Animals ; Mice ; Checkpoint Kinase 1/genetics ; Checkpoint Kinase 1/metabolism ; Mercaptoethanol/metabolism ; Ataxia Telangiectasia Mutated Proteins/genetics ; Ataxia Telangiectasia Mutated Proteins/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Up-Regulation ; Ataxia Telangiectasia/metabolism ; Antioxidants/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase ; DNA Damage ; Phosphorylation ; Reperfusion Injury/prevention & control ; Reperfusion Injury/metabolism ; Kidney/metabolism ; DNA/metabolism ; Ischemia/metabolism ; Cell Cycle Proteins/genetics
    Chemical Substances Checkpoint Kinase 1 (EC 2.7.11.1) ; Mercaptoethanol (60-24-2) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Tumor Suppressor Proteins ; Antioxidants ; Phospholipid Hydroperoxide Glutathione Peroxidase (EC 1.11.1.12) ; DNA (9007-49-2) ; Cell Cycle Proteins
    Language English
    Publishing date 2022-08-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2186248-5
    ISSN 2299-5684 ; 1734-1140
    ISSN (online) 2299-5684
    ISSN 1734-1140
    DOI 10.1007/s43440-022-00403-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Epoxyeicosatrienoic acid activation moderates endothelial mesenchymal transition to reduce obstructive nephropathy

    Babu J. Padanilam

    Kidney Research and Clinical Practice, Vol 36, Iss 4, Pp 299-

    2017  Volume 301

    Keywords Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher The Korean Society of Nephrology
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Renal sympathetic nerve activation via α

    Jang, Hee-Seong / Kim, Jinu / Padanilam, Babu J

    Kidney research and clinical practice

    2019  Volume 38, Issue 1, Page(s) 6–14

    Abstract: Chronic kidney disease (CKD) is increasing worldwide without an effective therapeutic strategy. Sympathetic nerve activation is implicated in CKD progression, as well as cardiovascular dysfunction. Renal denervation is beneficial for controlling blood ... ...

    Abstract Chronic kidney disease (CKD) is increasing worldwide without an effective therapeutic strategy. Sympathetic nerve activation is implicated in CKD progression, as well as cardiovascular dysfunction. Renal denervation is beneficial for controlling blood pressure (BP) and improving renal function through reduction of sympathetic nerve activity in patients with resistant hypertension and CKD. Sympathetic neurotransmitter norepinephrine (NE) via adrenergic receptor (AR) signaling has been implicated in tissue homeostasis and various disease progressions, including CKD. Increased plasma NE level is a predictor of survival and the incidence of cardiovascular events in patients with end-stage renal disease, as well as future renal injury in subjects with normal BP and renal function. Our recent data demonstrate that NE derived from renal nerves causes renal inflammation and fibrosis progression through alpha-2 adrenergic receptors (α
    Language English
    Publishing date 2019-03-04
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2656420-8
    ISSN 2211-9132
    ISSN 2211-9132
    DOI 10.23876/j.krcp.18.0143
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  8. Article: Defective Mitochondrial Fatty Acid Oxidation and Lipotoxicity in Kidney Diseases.

    Jang, Hee-Seong / Noh, Mi Ra / Kim, Jinu / Padanilam, Babu J

    Frontiers in medicine

    2020  Volume 7, Page(s) 65

    Abstract: The kidney is a highly metabolic organ and uses high levels of ATP to maintain electrolyte and acid-base homeostasis and reabsorb nutrients. Energy depletion is a critical factor in development and progression of various kidney diseases including acute ... ...

    Abstract The kidney is a highly metabolic organ and uses high levels of ATP to maintain electrolyte and acid-base homeostasis and reabsorb nutrients. Energy depletion is a critical factor in development and progression of various kidney diseases including acute kidney injury (AKI), chronic kidney disease (CKD), and diabetic and glomerular nephropathy. Mitochondrial fatty acid β-oxidation (FAO) serves as the preferred source of ATP in the kidney and its dysfunction results in ATP depletion and lipotoxicity to elicit tubular injury and inflammation and subsequent fibrosis progression. This review explores the current state of knowledge on the role of mitochondrial FAO dysfunction in the pathophysiology of kidney diseases including AKI and CKD and prospective views on developing therapeutic interventions based on mitochondrial energy metabolism.
    Language English
    Publishing date 2020-03-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2020.00065
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Renal Sympathetic Nerve-Derived Signaling in Acute and Chronic kidney Diseases.

    Noh, Mi Ra / Jang, Hee-Seong / Kim, Jinu / Padanilam, Babu J

    International journal of molecular sciences

    2020  Volume 21, Issue 5

    Abstract: The kidney is innervated by afferent sensory and efferent sympathetic nerve fibers. Norepinephrine (NE) is the primary neurotransmitter for post-ganglionic sympathetic adrenergic nerves, and its signaling, regulated through adrenergic receptors (AR), ... ...

    Abstract The kidney is innervated by afferent sensory and efferent sympathetic nerve fibers. Norepinephrine (NE) is the primary neurotransmitter for post-ganglionic sympathetic adrenergic nerves, and its signaling, regulated through adrenergic receptors (AR), modulates renal function and pathophysiology under disease conditions. Renal sympathetic overactivity and increased NE level are commonly seen in chronic kidney disease (CKD) and are critical factors in the progression of renal disease. Blockade of sympathetic nerve-derived signaling by renal denervation or AR blockade in clinical and experimental studies demonstrates that renal nerves and its downstream signaling contribute to progression of acute kidney injury (AKI) to CKD and fibrogenesis. This review summarizes our current knowledge of the role of renal sympathetic nerve and adrenergic receptors in AKI, AKI to CKD transition and CKDand provides new insights into the therapeutic potential of intervening in its signaling pathways.
    MeSH term(s) Acute Kidney Injury/metabolism ; Animals ; Humans ; Kidney/innervation ; Receptors, Adrenergic/metabolism ; Renal Insufficiency, Chronic/metabolism ; Signal Transduction ; Sympathetic Nervous System/metabolism
    Chemical Substances Receptors, Adrenergic
    Language English
    Publishing date 2020-02-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21051647
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  10. Article ; Online: Repeated Administration of Cisplatin Transforms Kidney Fibroblasts through G2/M Arrest and Cellular Senescence

    Jia-Bin Yu / Dong-Sun Lee / Babu J. Padanilam / Jinu Kim

    Cells, Vol 11, Iss 3472, p

    2022  Volume 3472

    Abstract: Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer, but it has nephrotoxic side effects leading to acute kidney injury and subsequently chronic kidney disease (CKD). Previous work has focused on acute kidney tubular ... ...

    Abstract Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer, but it has nephrotoxic side effects leading to acute kidney injury and subsequently chronic kidney disease (CKD). Previous work has focused on acute kidney tubular injury induced by cisplatin, whereas the chronic sequelae post-injury has not been well-explored. In the present study, we established a kidney fibroblast model of CKD induced by repeated administration of cisplatin (RAC) as a clinically relevant model. In NRK-49F rat kidney fibroblasts, RAC upregulated α-smooth muscle actin (α-SMA) and fibronectin proteins, suggesting that RAC induces kidney fibroblast-to-myofibroblast transformation. RAC also enhanced cell size, including the cell attachment surface area, nuclear area, and cell volume. Furthermore, RAC induced p21 expression and senescence-associated β-galactosidase activity, suggesting that kidney fibroblasts exposed to RAC develop a senescent phenotype. Inhibition of p21 reduced cellular senescence, hypertrophy, and myofibroblast transformation induced by RAC. Intriguingly, after RAC, kidney fibroblasts were arrested at the G2/M phase. Repeated treatment with paclitaxel as an inducer of G2/M arrest upregulated p21, α-SMA, and fibronectin in the kidney fibroblasts. Taken together, these data suggest that RAC transforms kidney fibroblasts into myofibroblasts through G2/M arrest and cellular senescence.
    Keywords cisplatin ; kidney fibroblast ; myofibroblast ; senescence ; cell cycle ; p21 ; Biology (General) ; QH301-705.5
    Subject code 500 ; 616
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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