Poli (Adp-riboz) polimeraz (Parp) inhibitörlerinin önemi

Poli (ADP-riboz) sentetaz (PARS) adıyla da bilinen poli (ADP-riboz) polimeraz (PARP), deoksiribonükleik asid (DNA) onarımı, gen transkripsiyonu' hücre ölümü, kromatin fonksiyonu ve gen stabilitesi gibi birçok hücresel sürecin düzenlenmesinde rol oynayan nükleer bir enzimdir. Çeşitli durumlarda oksijen ve nitrojen kaynaklı radikallerin indüklediği DNA tekli zincir kırıkları PARP enzim aktivitesinde artışa neden olmakta ve hücresel fonksiyon bozuklukları ve ölümle sonuçlanmaktadır. Myokardiyal reperfüzyon hasarı, inme, şok, diyabet ve yaşlanmaya bağlı kardiyovasküler fonksiyon bozuklukları, kronik kalp yetmezliği, ilaçla-indüklenen kalp yetmezliği, kalp transplantasyonu sonrası reperfüzyon hasarı ve hiper-homosisteinemiye bağlı kardiyovasküler fonksiyon bozuklukları gibi klinik patofizyolojik koşullarda doku hasarının gelişimi açısından PARP yolağının aşırı aktivasyonu yeni ve önemli bir mekanizmayı sunmaktadır. Bu nedenle, bu yolağın PARP-inhibitörü ajanlarla inhibe edilmesi birçok kardiyovasküler ve inflamatuvar hastalığın tedavisinde yeni bir terapötik yaklaşıma yol açabileceği gibi aynı zamanda antitümör ajanların sitotoksitesini de arttırabilir.

Anahtar Kelimeler:

Hiperhomosisteinemi, Adenozin difosfat riboz, Oksidatif stres, Poly(ADP-riboz) Polymerazlar, DNA, Transkripsiyon, genetik, Miyokardiyal reperfüzyon hasarı, Kalp yetmezliği, konjestif, Diabetes mellitus, Yaşlanma, Neoplazmlar

Importance of the poly (Adp-ribose) polymerase (Parp) inhibitors

Poly (ADP-Ribose) polymerase (PARP), also known as poly (ADP-ribose) synthetase (PARS), is a nuclear enzyme that is involved in the regulation of many cellular processes such as DNA repair, gene transcription, cell cycle progression, cell death, chromatin function, and genomic stability. In several conditions, oxygen- and nitrogen-derived radical-induced DNA single-strand breaks caused PARP overactivation, and results in cellular dysfuncyion and death. Ovefactivation of PARP represents an important novel mechanism of cell dysfunction in various pathophysiologic conditions, including myocardial reperfusion injury, circulatory shock, stroke, diabetes mellitus, hyperhomocysteinemia, aging, chronic heart failure, and drug-induced heart failure. Hence, inhibition of this pathway by PARP-inhibitor agents may represent a novel therapeutic approach for the treatment of various cardiovascular and inflammatory diseases. Also, pharmacological inhibitors of PARP may be able to enhance the cytotoxicity of antitumor agents.

Keywords:

Hyperhomocysteinemia, Adenosine Diphosphate Ribose, Oxidative Stress, Poly(ADP-ribose) Polymerases, DNA, Transcription, Genetic, Myocardial Reperfusion Injury, Heart Failure, Congestive, Diabetes Mellitus, Aging, Neoplasms,

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