Protein Kinaz C Aktivatörü PMA’nın TRPV1 Kanalları Üzerindeki Etkileri

Year 2015, Issue: 1, 42 - 73, 01.01.2015

Cemil Özgül

Abstract

TRP alt ailesinin bir üyesi olarak bilinen TRPV1 kanalları non-selektif katyon kanallarıdır. Bu kanalların en fazla bulunduğu dokular; arka kök gangliyon nöronları, vagal nöronlar ve trigeminal gangliyon nöronlarıdır. TRPV1 sıcaklık değişimi, düşük pH, kırmızı acı biberden elde edilen kapsaisin maddesi ile aktive olmaktadır. Bu kanalın sıcaklıkla aktive olması hücrede adeta termometre vazifesini gören kanal olarakta düşünülmesine sebep olmaktadır. Kapsaisin reseptörü olarak da bilinen TRPV1’in özel kapatıcısı ise kapsazepin maddesidir. Vücud aktivitelerinin devamını sağlayan en önemli unsurlardan biri; birincil haberci hormonlar ve nörotransmitter maddeler ve ikincil haberci sistemleridir. İç salgı bezlerinden salınan hormonlar hedef hücreye ulaştığında kendine özgü reseptörlere bağlanır ve ikincil haberci sistemini aktif hale getirir. Bu ikincil haberci sistemlerinin en önemlilerinden biri, PLC aktivasyonu yoluyla PKC aktivasyonudur. Ayrıca, PKC hücre içi Ca+2 miktarı arttıkça da aktive olmaktadır. Aynı zamanda, forbol esterler içinde en iyi bilinen PMA maddesi de doğrudan PKC’yi aktif hale getirmektedir. PKC ise TRPV1 kanallarının bazı özel bölgelerine bağlanarak kanalı aktif hale getirir. Hücre içi Ca+2 miktarı arttıkça oksidatif stresin de artacağı iyi bilinmektedir. TRPV1’in aktive olmasıyla daha fazla hücre içi Ca+2 miktarı artacak, artan Ca+2 miktarı ile de daha fazla PKC aktivasyonu olacaktır. Pozitif geribildirim mekanizması gibi bu süreç devam ederken, hücre içi oksidatif stres aşırı derecede fazlalaşacaktır. Eğer antioksidan sistem devreye girmez veya yetersiz kalırsa hücre apopitozise kadar devam edebilecektir. Sinir hücrelerinde, PKC aktivasyonu ile TRPV1’in açılıp hücre içerisindeki Ca+2 konsantrasyonunun fizyolojik koşulların ötesine geçmesi, fazla Ca+2 miktarına bağlı birçok hastalığın tetikçisi olabileceği düşünülmektedir. Bu hastalıkların tedavisinde PKC yoluyla TRPV1 kanalları üzerinden Ca+2 akışının durdurulmak istenmesi gayet tabiidir. Bu konuyla ilgili sınırlı sayıda çalışma bulunmasından dolayı, antioksidan maddelerin bu mekanizma üzerinden aktive olan TRPV1 kanal inhibisyonuna etkisinin araştırılması, nörolojik hastalıkların tedavisinin etiyolojisine büyük katkı sağlayacaktır.

Keywords

TRPV1 Kanal Agonist ve Antagonistleri, Protein Kinaz C, İkinci Haberciler, Oksidatif Stres, Sinir Hücreleri

Effects of Protein Kinase C Activator PMA on TRPV1 Channels

Abstract

TRPV1 channel, which is one of TRP super families, is a non- selective cation channel. An important part of the TRPV1 channel is located in dorsal root ganglion, vagal and trigeminal neurons. TRPV1 is activated by high temperatures, low pH and capsaicin isolated from red hot chili peppers. The activation of this channel is via temperature hence it functions in the neurons like a thermometer. Also, the chemical capsazepine is a specific blocker of TRPV1. One of the most important events for the activities in the body is primary and secondary hormones and neurotransmitters messenger systems. Hormones are released by endocrine glands and they bind a specific receptor. When the hormone binds to its receptor, it leads to the release of the secondary messenger. One of the most important secondary messengers is PKC via activation of PLC. When Ca2+ ions levels are elevated in the cell, it causes the increase of the PKC levels, as well. Also, PMA agent is a phorbol ester, directly activates PKC, which in turn induces TRPV1 channels. It is well known that an increase in the amount of intracellular Ca2+ leads to an increase in oxidative stress. The activation of TRPV1 increases further the amount of intracellular Ca2+ and an increase by means of the amount of Ca2+ causes more activation of PKC. While this process continues as a positive feedback mechanism, the oxidative stress will continue to increase. If the antioxidant system is not activated or is insufficient, the cell will be directed to apoptosis. Ca2+ concentration as a result of the opening of TRPV1 via PKC activation and going beyond physiological conditions in the nerve cells can lead to a lot of diseases. In treatment of these diseases, stopping the flowing of Ca2+ via TRPV1 and activation of PKC request is self-evident. Due to the presence of a limited number of studies on this topic, investigation of the effects of antioxidant substances inhibition of TRPV1 channel activated by this mechanism will contribute to the etiology of neurological disorders’ treatment.

Keywords

TRPV1 Channel Agonists and Antagonists, Protein Kinase C, Secondary Messengers, Oxidative Stress, Nerve Cells

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