Rho Kinaz ve Apoptoz

Öz

AbstractRho Kinase and Apoptosis Apoptosis, programmed cell death, is characterized by several morphological changes. Cysteine-proteases called caspases are responsible for those apoptotic morphological changes including membrane blebbing, chromatin condensation, DNA disintegration and cell fragmentation. Apoptosis develops during lifetime and has an important role in normal tissue homeostasis. Moreover, apoptosis contributes to several pathological conditions including AIDS, Alzheimer, autoimmune syndromes and cardiovascular diseases. Small G protein Rho mediates several intracellular mechanisms. In the middle of 1990\'s two effectors of Rho, ROKα/ROCK II and ROKβ /ROCK I (Rho kinase), were identified. It was shown that Rho kinases contribute to physiological functions such as blood pressure homeostasis, smooth muscle contraction, cell proliferation, adhesion, migration and inflammatory response. Recent studies showed that two ROCK isoforms, ROCK I and ROCK II, are involved in the regulation of apoptosis. ROCK I and ROCK II were shown to be cleaved and activated in the execution phase of apoptosis. Activated ROCK-induced myosin light chain phosphorylation increases membrane blebbing. ROCK also has roles in other processes of apoptosis such as fragmentation and phagocytosis of apoptotic bodies. Identifiying possible involvement of ROCK in the regulation of apoptosis can be helpful in treating several diseases such as cancer and cardiovascular disorders. This review focuses on understanding of ROCK signaling in the regulation of apoptosis.

Anahtar Kelimeler

• apoptosis, Rho-associated kinases, ROCK I, ROCK II

Rho Kinaz ve Apoptoz

Öz

Programlı hücre ölümü olarak bilinen apoptoz, çeşitli morfolojik değişimlerle karakterizedir. Sistein proteaz olan kaspazlar, membran tomurcuklanması, kromatin yoğunlaşması, DNA disintegrasyonu ve hücre parçalanması gibi apoptotik morfolojik değişimlerden sorumludur. Apoptoz, yaşamın her aşamasında gelişir ve normal doku homeostazında önemli bir rolü vardır. Bunun yanı sıra apoptoz, AIDS, Alzheimer, otoimmün hastalıklar ve bazı kardiyovasküler hastalıkları gibi birçok patolojik durumlara da eşlik eder. Hücre içi birçok sinyalleme mekanizmalarına aracılık eden küçük bir G proteini olan Rho'nun, 1990'ların ortalarında iki efektörü tanımlanmıştır. Bunlar ROKα/ROCK II ve ROKβ/ROCK I (Rho kinazlar)'dır. Rho kinazların kan basıncı homeostazı, düz kas kontraksiyonu, hücre proliferasyonu, hücre adezyonu, migrasyonu ve inflamatuvar cevabı da içeren çok sayıda önemli fizyolojik işlevlere katıldığı gösterilmiştir. Yapılan çalışmalarda, ROCK I ve ROCK II'nin apoptozun düzenlenmesinde etkili olduğu görülmüştür. ROCK I ve ROCK II'nin apoptozun işlem fazında ("execution phase") kesilip etkinleştiği gösterilmiştir. Etkin ROCK'nin indüklediği miyozin hafif zincir fosforilasyonu membran tomurcuk oluşumuna neden olmaktadır. Ayrıca ROCK'nin hücre parçalanması ve apoptotik cisimciklerin fagositozu gibi apoptozun öteki basamaklarında da etkili olduğu bilinmektedir. Apoptozun biyokimyasal yollarının anlaşılması kanser ve kardiyovasküler bozukluklar gibi etiyolojisi tam olarak bilinmeyen birçok hastalığın tedavisi için yararlı olabilir. Bu derlemede apoptozun düzenlenmesinde ROCK sinyalizasyonunun anlaşılmasına odaklanılmıştır.

Anahtar Kelimeler

• apoptosis, Rho-associated kinases, ROCK I, ROCK II

Kaynakça

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