Poly (ADP-ribose) polymerase-1 initiated neuronal cell death pathway—do androgens matter?

Vagnerova, Kamila; Liu, K.; Ardeshiri, Ardi; Cheng, Jian; Murphy, Stephanie J.; Hurn, Patricia D.; Herson, Paco S.

doi:10.1016/j.neuroscience.2009.12.041

Cited by 37 publications

(38 citation statements)

References 34 publications

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“…Moreover, PARP-1 regulates the progression of autoimmune nephritis in males by inducing necrotic cell death and modulating inflammation 65 ; PARP-1-mediated cell death is sexually dimorphic, participating in ischemic damage in the male, but not the female, brain. 125 Because vitamin D can act as a PARP-1 inhibitor, and estrogen shares some structural properties with vitamin D, it is possible that protection from PARP-1 overactivation is afforded by estrogen in females (to be validated in future studies).…”

Section: Discussionmentioning

confidence: 99%

Signaling Mechanism of Poly(ADP-Ribose) Polymerase-1 (PARP-1) in Inflammatory Diseases

Garg

2011

The American Journal of Pathology

163

140

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Poly(ADP-ribosyl)ation, attaching the ADP-ribose polymer chain to the receptor protein, is a unique posttranslational modification. Poly(ADP-ribose) polymerase-1 (PARP-1) is a well-characterized member of the PARP family. In this review, we provide a general update on molecular structure and structure-based activity of this enzyme. However, we mainly focus on the roles of PARP-1 in inflammatory diseases. Specifically, we discuss the signaling pathway context that PARP-1 is involved in to regulate the pathogenesis of inflammation. PARP-1 facilitates diverse inflammatory responses by promoting inflammation-relevant gene expression, such as cytokines, oxidation-reductionrelated enzymes, and adhesion molecules. Excessive activation of PARP-1 induces mitochondria-associated cell death in injured tissues and constitutes another mechanism for exacerbating inflammation. There are many posttranslational protein modifications (eg, phosphorylation, acetylation, methylation, and ubiquitylation) that are involved in a wide scope of cellular processes, including chromatin remodeling, transcriptional regulation, and signal transmission response to extracellular stimulation. Poly(ADP-ribosyl)ation (PARylation) is one of such essential protein modifications, whereby polymers of ADP-ribose (PARs) are formed from donor NAD ϩ molecules and covalently attached via an ester linkage to glutamic acid and less commonly to aspartic acid or lysine of target proteins.1-3 The target proteins generally contain a PAR-binding consensus motif that frequently overlaps with a functional domain, such as a protein-or DNA-binding domain (DBD), and thus accounts for PAR modification, altering the functional properties of the targets. 4 The process of PARylation is catalyzed by the poly-(ADP-ribose) polymerase (PARP) family of enzymes that consists of 18 members. 5 The PARPs, historically known as poly(ADP-ribose) synthases and poly(ADP-ribose) transferases, 6,7 show different structure, cellular location, and functions. 8,9 Only two members of this family (ie, PARP-1 and PARP-2) are DNA damage related; and PARP-1, the best-understood member, is an abundant nuclear enzyme and accounts for at least 85% of the cellular PARP activity. 10Since the discovery of PAR synthesis and PARP-1 decades ago, 11,12 new discoveries have been consistently published related to their structure, property, and functions. PARP-1 is a multifunctional enzyme and has a key role in the spatial and temporal organization of DNA repair, thus maintaining genome integrity and facilitating cell survival. PARP-1 catalyzes the synthesis and attachment of highly negatively charged PARs to target proteins, including histones, topoisomerases, DNA helicases, and single-strand break repair and base excision repair factors; and facilitates relaxation of the chromatin superstructure, protein-protein interaction, and DNAbinding ability of the members of the DNA repair machinery. A recently published article 13 reviews the role of PARP-1 in DNA repair. In addition, the importance of poly-(ADP-...

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Section: Discussionmentioning

confidence: 99%

Signaling Mechanism of Poly(ADP-Ribose) Polymerase-1 (PARP-1) in Inflammatory Diseases

Garg

2011

The American Journal of Pathology

163

140

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“…30 Briefly, mice were anesthetized with isoflurane (induction 3.0% and maintenance 1.5% to 2.0%, delivered through a face mask in oxygenenriched air). Head and body temperature was monitored and maintained at 36.5 ± 1.01C throughout the MCAO surgery with an electrical heating pad and heating lamp.…”

Section: Middle Cerebral Artery Occlusion Modelmentioning

confidence: 99%

“…The LC mobile phase consisted of 2 mmol/L dibutylammonium formate buffer (pH 6.5) in water (mobile A) and methanol (mobile B). The following LC gradient was run at 0.6 mL/minute: 0 to 1 minute: 95% mobile A; 1 to 3 minutes: 95% to 70% mobile A; 3 to 10 minutes: 70% to 45% mobile A; 10 to 14 minutes: 45% to 10% mobile A; 14 to 14.8 minutes: 10% 30, and so was the heater gas (both nitrogen). The collision gas and curtain gas were at 10 and 20, respectively (both nitrogen).…”

Section: Infarct Volume Analysismentioning

confidence: 99%

Androgen and PARP-1 Regulation of TRPM2 Channels after Ischemic Injury

Shimizu

Macey

Quillinan

et al. 2013

J Cereb Blood Flow Metab

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The calcium-permeable transient receptor potential M2 (TRPM2) ion channel was recently demonstrated to have a sexually dimorphic contribution to ischemic brain injury, with inhibition or knockdown of the channel protecting male brain preferentially. We tested the hypothesis that androgen signaling is required for this male-specific cell-death pathway. Additionally, we tested the hypothesis that differential activation of the enzyme poly (ADP-ribose) polymerase-1 (PARP-1) is responsible for male-specific TRPM2 channel activation and neuronal injury. We observed that administration of the TRPM2 inhibitor clotrimazole (CTZ) 2 hours after onset of ischemia reduced infarct volume in male mice and that protection from ischemic damage by CTZ was abolished by removal of testicular androgens (castration; CAST) and rescued by androgen replacement. Male PARP-1 knockout mice had reduced ischemic damage compared with WT mice and inhibition of TRPM2 with CTZ failed to reduce infarct size. Lastly, we observed that ischemia increased PARP activity in the peri-infarct region of male mice to a greater extent than female mice and the difference was abolished in CAST male mice. Data presented in the current study indicate that TRPM2-mediated neuronal death in the male brain requires intact androgen signaling and PARP-1 activity.

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“…It has reported that PARP-1 mostly plays a key role in cell death following numerous inflammation situations such as ischemia reperfusion damage [61], haemorrhagic shock, septic shock [62], lung inflammation [63], diabetes mellitus [64], autoimmune nephritis [65], chronic inflammatory disorders such as arthritis and IBD [66], and diseases of the central nervous system [67]. PARP-1-deficient mice showed decreased PARP-1 expression, a significant parameter in the endothelial dysfunction pathogenesis of diabetes [64], regulates the progression of autoimmune nephritis [65].…”

Section: The Role Of Nfkb1 and Parp-1 Inflammatory Diseasementioning

confidence: 99%

A General Sight about Linking PARP-1 and NFKB1 Variations to the Inflammatory Events

Gk¹,

Yenmiş²,

Koc³

2014

Interdiscip J Microinflammation

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Poly (ADP-ribose) polymerase-1 (PARP-1) has various roles in cellular processes such as DNA repair, genomic stability, transcription, stress response, and cell death via regulating death and inflammation signalling pathways. On the other hand, PARP-1 inhibition has been shown to provide benefits in experimental models of animals with inflammatory diseases such as asthma, atherosclerosis and diabetes. PARP-1 also acts a transcriptional coactivator of nuclear factor kappa B (NFKB). The NFKB is a ubiquitous transcription factor that controls the expression of genes encoding cell adhesion molecules, growth factors, cytokines, and some acute phase proteins. Inappropriate activation of NFKB has been mostly searched with inflammatory events. In complete and persistent inhibition studies of NFKB, apoptosis, inappropriate immune cell development and delayed cell growth were investigated. These findings might provide new perceptions in the pathogenesis of inflammatory disorders regarding the roles of PARP-1 and NFKB1 proteins. In this review, we focus on some variations (rs28362491, rs696, rs1136410, rs2793378, rs7527192) of PARP-1 and NFKB1 genes in relation to susceptibility to common inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, allergic rhinitis, Graves' disease, Hashimoto's thyroiditis, asthma and Behcet's disease.

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Poly (ADP-ribose) polymerase-1 initiated neuronal cell death pathway—do androgens matter?

Cited by 37 publications

References 34 publications

Signaling Mechanism of Poly(ADP-Ribose) Polymerase-1 (PARP-1) in Inflammatory Diseases

Signaling Mechanism of Poly(ADP-Ribose) Polymerase-1 (PARP-1) in Inflammatory Diseases

Androgen and PARP-1 Regulation of TRPM2 Channels after Ischemic Injury

A General Sight about Linking PARP-1 and NFKB1 Variations to the Inflammatory Events

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