Poly(ADP-ribose) Polymerases

Publication Title: 
The EMBO journal

Telomere loss has been proposed as a mechanism for counting cell divisions during aging in normal somatic cells. How such a mitotic clock initiates the intracellular signalling events that culminate in G1 cell cycle arrest and senescence to restrict the lifespan of normal human cells is not known. We investigated the possibility that critically short telomere length activates a DNA damage response pathway involving p53 and p21(WAF1) in aging cells.

Author(s): 
Vaziri, H.
West, M. D.
Allsopp, R. C.
Davison, T. S.
Wu, Y. S.
Arrowsmith, C. H.
Poirier, G. G.
Benchimol, S.
Publication Title: 
Trends in Biochemical Sciences

Nicotinamide adenine dinucleotide (NAD(+)) is both a coenzyme for hydride-transfer enzymes and a substrate for NAD(+)-consuming enzymes, which include ADP-ribose transferases, poly(ADP-ribose) polymerases, cADP-ribose synthases and sirtuins. Recent results establish protective roles for NAD(+) that might be applicable therapeutically to prevent neurodegenerative conditions and to fight Candida glabrata infection.

Author(s): 
Belenky, Peter
Bogan, Katrina L.
Brenner, Charles
Publication Title: 
Journal of Ethnopharmacology

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. Bark. (EUE), has commonly been used to fortify the muscles and lungs, lower blood pressure, prevent miscarriage, improve the tone of liver and kidneys, and promote longevity the traditional tonic medicines of Korea, China, and Japan. AIM OF THE STUDY: In this study, we investigated that the neuroprotective activities and possible mechanisms of EUE aqueous extract in hydrogen peroxide (H(2)O(2))-induced neuronal cell death in human SH-SY5Y neuroblastoma cells.

Author(s): 
Kwon, Seung-Hwan
Kim, Min-Jung
Ma, Shi-Xun
You, In-Jee
Hwang, Ji-Young
Oh, Ji-Hwan
Kim, Sun-Yeou
Kim, Hyoung-Chun
Lee, Seok-Yong
Jang, Choon-Gon
Publication Title: 
Molecular Aspects of Medicine

Poly(ADP-ribosyl)ation (PARylation) is a posttranslational protein modification (PTM) catalyzed by members of the poly(ADP-ribose) polymerase (PARP) enzyme family. PARPs use NAD(+) as substrate and upon cleaving off nicotinamide they transfer the ADP-ribosyl moiety covalently to suitable acceptor proteins and elongate the chain by adding further ADP-ribose units to create a branched polymer, termed poly(ADP-ribose) (PAR), which is rapidly degraded by poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3 (ARH3).

Author(s): 
B¸rkle, Alexander
Vir·g, L·szlÛ
Publication Title: 
Clinical Cancer Research: An Official Journal of the American Association for Cancer Research

PURPOSE: Pancreatic cancer is the fourth cause of death from cancer in the western world. Majority of patients present with advanced unresectable disease responding poorly to most chemotherapeutic agents. Chemotherapy for pancreatic cancer might be improved by adjusting it to individual genetic profiles. We attempt to identify genetic predictors of chemosensitivity to broad classes of anticancer drugs.

Author(s): 
Cui, Yunfeng
Brosnan, Jacqueline A.
Blackford, Amanda L.
Sur, Surojit
Hruban, Ralph H.
Kinzler, Kenneth W.
Vogelstein, Bert
Maitra, Anirban
Diaz, Luis A.
Iacobuzio-Donahue, Christine A.
Eshleman, James R.
Publication Title: 
European Journal of Pharmacology

Bioactive compounds found in many plant species have been used in Chinese, Unani, and Indian ayurvedic medicine. Accumulative evidences in both in vitro and in vivo studies using berberine demonstrated anti-cancer and anti-inflammatory properties in different cancer cells. In the present study, a putative compound from commercial sample was purified by chromatographic techniques. The structure of the pure compound was confirmed by spectroscopic studies.

Author(s): 
Patil, Jeevitha B.
Kim, Jinhee
Jayaprakasha, G. K.
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

In diabetes, activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an important effector of oxidative-nitrosative injury, which contributes to the development of experimental diabetic peripheral neuropathy (DPN). However, the potential toxicity of complete PARP inhibition necessitates the utilization of weaker PARP inhibitors with additional therapeutic properties. Nicotinamide (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can improve energy status and inhibit cell death in ischemic tissues.

Author(s): 
Stevens, M. J.
Li, F.
Drel, V. R.
Abatan, O. I.
Kim, H.
Burnett, D.
Larkin, D.
Obrosova, I. G.
Publication Title: 
Journal of Pineal Research

Prostate cancer (PCa) is a major age-related malignancy as increasing age correlates with increased risk for developing this neoplasm. Similarly, alterations in circadian rhythms have also been associated with the aging population and cancer risk. The pineal hormone melatonin is known to regulate circadian rhythms, which is under the control of a core set of genes: Period 1, 2, 3 (Per 1-3); Cryptochrome 1, 2 (Cry 1, 2); Clock, and Bmal 1, 2.

Author(s): 
Jung-Hynes, Brittney
Huang, Wei
Reiter, Russel J.
Ahmad, Nihal
Publication Title: 
PloS One

Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited.

Author(s): 
Wang, Lihong
Liu, Liping
Shi, Yan
Cao, Hanwei
Chaturvedi, Rupesh
Calcutt, M. Wade
Hu, Tianhui
Ren, Xiubao
Wilson, Keith T.
Polk, D. Brent
Yan, Fang
Publication Title: 
Neurochemistry International

Lanthionines are novel neurotrophic and neuroprotective small molecules that show promise for the treatment of neurodegenerative diseases. In particular, a recently developed, cell permeable lanthionine derivative known as LKE (lanthionine ketimine 5-ethyl ester) promotes neurite growth at low nanomolar concentrations. LKE also has neuroprotective, anti-apoptotic, and anti-inflammatory properties. Its therapeutic potential in cerebral ischemia and its mechanisms of neurotrophic action remain to be fully elucidated.

Author(s): 
Nada, Shadia E.
Tulsulkar, Jatin
Raghavan, Aparna
Hensley, Kenneth
Shah, Zahoor A.

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