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İskemik ön koşullanma ve sonradan koşullanma mekanizmaları olarak intraselüler sinyalizasyon ve adenozin

Yıl 2010, Cilt: 32 Sayı: 1, 127 - 131, 11.03.2010

İlker Şengül Demet Şengül

Öz

Özet

İskemi reperfüzyon hasarı, deoksijene dokunun resirkülasyonu sırasında oluşan patofizyolojik değişiklikler serisidir. İskemi reperfüzyon hasarının potansiyel mekanizması; hipoksiyi, reperfüzyon ile salınan serbest oksijen radikallerini ve inflamatuvar medyatörleri içermektedir. Primer iskemik hasar; son ürünlerin ve kan akımının azalmasına bağlı oluşan anaerobik metabolizmanın toksik ürünlerinin birikimi sonucunda ortaya çıkmaktadır. Ancak, reperfüzyon hasarı nda, serbest oksijen radikallerinin, doku hasarına doğrudan kendileri etkiyerek ve hücresel antioksidan sistemleri yetersizleştirmesi yatmaktadır. İskemik ön koşullanmada lokal olarak salınan agonistler; sinyalizasyon yolunu, G proteinine bağlı olan reseptörlerin aktivasyonu yoluyla tetikler. İskemik ön koşullanma yoluyla olan adaptasyon; adenozin etkisi ile oluşan, KATP (Potasyum-ATP) kanal aktivasyonu tarafından yaratılır. İskemik sonradan koşullanmanın ise; ERK ½ (Ekstraselüler sinyal regüle kaskad ½)  ile mitokondriyal KATP kanallarının aktivasyonuna ve NO (Nitrik oksit) üretimine bağlı olduğu ve anılan fenomenin koruyucu etkisi için adenozin reseptörlerinin kullanıldığı ve gunilil siklaz ile PI3 (Fosfatidil inozitol3)-kinaz aktivasyonuna gereksinim olduğu ileri sürülmüştür.

Anahtar sözcükler: Adenozin, intraselüler sinyalizasyon, iskemik, ön koşullanma, sonradan koşullanma.

 

Abstract

Ischemia reperfusion injury is the series of pathophysiological changes occurring in consequence of recirculation in the deoxygenated tissue. The potential mechanism of ischemia reperfusion injury includes tissue hypoxia, free oxygen radicals arising from the course of reperfusion, and inflammatory mediators. Primary ischemic injury appears as a consequence of accumulation of end products and toxic products of anaerobic metabolism which is occurred by insufficient circulation. But, in the concept of reperfusion injury; free oxygen radicals directly causes tissue injury via affecting themselves and producing inadequacy of cellular antioxidant systems. In ischemic pre - conditioning, locally released agonists trigger signalization way via activating receptors which are bounded to G protein. The adaptation via ischemic pre - conditioning is created by activation of KATP (Potassium-ATP) channels by the effect of adenosine. In the aspect of ischemic post - conditioning; it is propounded that this phenomenon depends on activation of mitochondrial KATP channels and ERK ½ (extracellular signal-regulated kinase cascade) and production of NO (Nitric oxide) and for the protective effect of the mentioned phenomenon, adenosine receptors are used and activation of PI3 (phosphatidyl inositol3) - kinase and guanylyl cyclase are needed.

Keywords: Adenosine, intracellular signalization, ischemic, preconditioning, post conditioning.

Anahtar Kelimeler

-

Kaynakça

  • Xu DZ, Lu Q, Kubicka R, Deitch EA. The effect of hypoxia/reoxgenation on the cellular function of intestinal epithelial cells. J Trauma 1999; 46: 280-5.
  • Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV. Multiple-organ-failure syndrome. Arch Surg 1986; 121: 196-208.
  • Armstrong SC. Protein kinase activation and myocardial ischemia- reperfusion injury. Cardiovasc Res 2004;61:427-36.
  • Murphy E. Pimary and secondary signaling pathways in early preconditioning converge in mitochondria to produce cardioprotection. Circ Res 2004; 94: 7-16.
  • Stumpner J, Redel A, Kellermann A, Lotz CA, Blomeyer CA, Smul TM, Kehl F, Roewer N, Lange M. Differential role of Pim-1 kinase in anesthetic-induced and ischemic preconditioning against myocardial infarction. Anesthesiology 2009;111:1257-64.
  • Sadat U. Signaling pathways of cardioprotective ischemic preconditioning. Int J Surg 2009;7:490-8.
  • Xuan YT, Guo Y, Zhu Y, Wang OL, Rokosh G, Messing RO, Bolli R. Role of the protein kinase C-epsilon-Raf-1-MEK-1/2-p44/42 MAPK signaling cascade in the activation of signal transducers and activators of transcription 1 and 3 and induction of cyclooxygenase-2 after ischemic preconditioning. Circulation 2005; 112: 1971-8.
  • Downey JM, Cohen MV. Arguments is favor of protein kinase C playing an important role in ischemic preconditioning. Basic Res Cardiol 1997; 92: 37-9.
  • Nishizuka Y. Intracellular signalling by hydrolysisof phospholipids and activation of protein kinase C. Science 1992;258:607-10.
  • Dreixler JC, Barone FC, Shaikh AR, Du E, Roth S. Mitogen-activated protein kinase p38alpha and retinal ischemic preconditioning. Exp Eye Res 2009; 89: 782-90.
  • Harun E, Dursun D, Ender S. İskemik ön koşullanma. Anadolu Kardiyol Derg 2003; 3 :144-9.
  • Miyawaki H, Ashraf M. Ca2+ as a mediator of ischemic preconditioning. Circ Res 1997; 80:790-4.
  • Rork TH, Wallace KL, Kennedy DP, Marshall MA, Lankford AR, Linden J. Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation. Am J Physiol Heart Circ Physiol 2008;295:H1825-33
  • Balakumar P, Singh H, Reddy K, Anand-Srivastava MB. Adenosine-A1 Receptors Activation Restores the Suppressed Cardioprotective Effects of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts. J Cardiovasc Pharmacol 2009; 54: 204-12.
  • Liu GS, Thornton J, Van Winkle DM, Stanley AM, Olsson RA, Downey JM. Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation 1991; 84: 350-6.
  • Baxter GF, Marber MS, Patel VC, Yellon DM. Adenosine receptor involvement in a delayed phose of myocardial protection 24 hours after ischemic preconditioning. Circulation 1994; 90: 2993-3000.
  • Wong J, Drake L, Sajjadi F, Fristen GS, Mullane KM, Bulloough DA. Dual activation of adenosine A1 and A3 receptors mediates preconditioning of isolated cardiac myocytes. Eur J Pharmacol 1997;320:241-8.
  • Claeys MJ, Vrints CJ, Bosmans JM, Conraads VM, Snoeck JP. Aminophylline inhibits adaptation to ischaemia during angioplasty. Role of adenosine in ischaemic preconditioning. Eur Heart J 1996;17:539-44.
  • Cleveland JC, Meldrum DR, Rowland RT, Banerjea A, Harken AH. Adenosine preconditioning of human myocardium is dependent upon the ATP-sensitive potassium channel. J Mol Cell Cardiol 1997; 29: 175-81.
  • Hausenloy DJ, Tsang A, Mocanu MM, Yellon DM. Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am J Physiol Heart Circ Physiol 2005 ; 288: 971-6.
  • Uchiyama T, Engelman RM, Maulik N, Das DK. Role of Akt signaling in mitochondrial survival pathway triggered by hypoxic preconditioning. Circulation. 2004;109:3042-9.
  • Krieg T, Qin Q, Philipp S, Alexeyev MF, Cohen MV, Downey JM. Acetylcholine and bradykinin trigger preconditioning in the heart through a pathway that includes Akt and NOS. Am J Physiol Heart Circ Physiol 2004; 287: 2606-11.
  • Tsang A, Hausenley DJ, Mocanu MM, Yellon DM. Postconditioning: a form of “modified reperfusion” protects myocardium by activating Phosphatidylinositol 3-kinase- Akt pathway. Cic Res 2004;95:230-2.
  • Yang X-M, Proctor JB, Cui L, Krieg T, Doney JM, Cohen MV. Multiple brief coronary occlusions during early reperfusion protects rabbit hearts by targeting cell signal pathways. J Am Coll 2004;44:1103-10.
  • Jiang ZS, Wen GB, Tang ZH, Srisakuldee W, Fandrich RR, Kardami E. High molecular weight FGF-2 promotes postconditioning-like cardioprotection linked to activation of the protein kinase C isoforms Akt and p70 S6 kinase. Can J Physiol Pharmacol 2009;87:798- 804.
  • Krolikowski JG, Weihrauch D, Bienengraeber M, Kersten JR, Warltier DC, Pagel PS. Role of Erk1/2, p70s6K, and eNOS in isoflurane-induced cardioprotection during early reperfusion in vivo. Can J Anaesth 2006;53:174-82.
  • Yang XM, Downey JM, Cohen MV. Postconditioning’s protection is not depended on circulating blood factors or cells but requires PI3-kinase and guanyl cyclase activation. Cicrulation 2004; 110;111-68.
  • Xu Z, Yang X-M, Cohen MV, Neumann T, Heush G, Downey JM. Limitation of infarct size in rabbit hearts by the novel adenosine receptor agonist AMP 579 administrted at reperfusion. J Moll Cell Cardiol 2000;32:2339-47.
  • Yang X-M, Krieg T,Cui L, Downey JM, Cohen MV. NECA and bradykinin reperfusion reduce infarction in rabbit hearts by signaling hrough PI3K, ERK and NO. J Moll Cell Cardiol 2004;36:411-21.
  • Danielisová V, Gottlieb M, Némethová M, Burda J. Effects of bradykinin postconditioning on endogenous antioxidant enzyme activity after transient forebrain ischemia in rat. Neurochem Res 2008;33:1057-64.
  • Jonassen AK, Sack MN, Mjos OD, Yellon DM. Myocardial protectionby insulin requires early administration and is mediated via Akt and p70S6 kinase cell-survival signaling. Circ Res 2001;89:1191-8.
  • Gross ER, Hsu AK, Gross GJ. Opioid induced cardioprotection occurs via glycogen synthase kinase beta inhibition during reperfusion in intact rat hearts. Circ Res 2004;94:960-6.

TWO OF THE MECHANISMS OF ISCHEMIC PRECONDITIONING AND POSTCONDITIONING: INTRACELLULAR SIGNALIZATION AND ADENOSINE.

Yıl 2010, Cilt: 32 Sayı: 1, 127 - 131, 11.03.2010

İlker Şengül Demet Şengül

Öz

          Ischemia reperfusion injury is the series of pathophysiological changings occuring in consequence of recirculation in the deoxygenated tissue. The potential mechanism of I/R injury includes tissue hypoxia, arising of free oxygen radicals in the course of reperfusion and occuring of inflammatory mediators. Primary ischemic injury appears as a consequence of accumulation of end products and toxic products of anaerobic metabolism which depending on decreasing in blood circulation and insufficient oxygenation. But, in the concept of reperfusion injury; free oxygen radicals causes tissue injury directly via affecting themselves and producing inadequacy of cellular antioxydant systems.

          In ischemic preconditioning, locally released agonists triggers signalization way via activating receptors which are bounded to G protein. The adaptation via ischemic preconditioning is created by activation of KATP (Potassium – ATP) channels by the effect of adenosine.

         In the aspect of ischemic postconditioning; it is propounded is depended on activation of mitochondrial KATP channels and ERK ½ (extracellular signal-regulated kinae cascade) and production of NO (Nitric oxide) and for the protective effect of the mentioned phenomenon, adenosine receptors are used and activation of PI3 (Phosphatidyl inositol3) - kinase and guanylyl cyclase are needed.

 

 

 

Anahtar Kelimeler

Adenozin intraselüler sinyalizasyon iskemik ön koşullanma sonradan koşullanma

Kaynakça

  • Xu DZ, Lu Q, Kubicka R, Deitch EA. The effect of hypoxia/reoxgenation on the cellular function of intestinal epithelial cells. J Trauma 1999; 46: 280-5.
  • Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV. Multiple-organ-failure syndrome. Arch Surg 1986; 121: 196-208.
  • Armstrong SC. Protein kinase activation and myocardial ischemia- reperfusion injury. Cardiovasc Res 2004;61:427-36.
  • Murphy E. Pimary and secondary signaling pathways in early preconditioning converge in mitochondria to produce cardioprotection. Circ Res 2004; 94: 7-16.
  • Stumpner J, Redel A, Kellermann A, Lotz CA, Blomeyer CA, Smul TM, Kehl F, Roewer N, Lange M. Differential role of Pim-1 kinase in anesthetic-induced and ischemic preconditioning against myocardial infarction. Anesthesiology 2009;111:1257-64.
  • Sadat U. Signaling pathways of cardioprotective ischemic preconditioning. Int J Surg 2009;7:490-8.
  • Xuan YT, Guo Y, Zhu Y, Wang OL, Rokosh G, Messing RO, Bolli R. Role of the protein kinase C-epsilon-Raf-1-MEK-1/2-p44/42 MAPK signaling cascade in the activation of signal transducers and activators of transcription 1 and 3 and induction of cyclooxygenase-2 after ischemic preconditioning. Circulation 2005; 112: 1971-8.
  • Downey JM, Cohen MV. Arguments is favor of protein kinase C playing an important role in ischemic preconditioning. Basic Res Cardiol 1997; 92: 37-9.
  • Nishizuka Y. Intracellular signalling by hydrolysisof phospholipids and activation of protein kinase C. Science 1992;258:607-10.
  • Dreixler JC, Barone FC, Shaikh AR, Du E, Roth S. Mitogen-activated protein kinase p38alpha and retinal ischemic preconditioning. Exp Eye Res 2009; 89: 782-90.
  • Harun E, Dursun D, Ender S. İskemik ön koşullanma. Anadolu Kardiyol Derg 2003; 3 :144-9.
  • Miyawaki H, Ashraf M. Ca2+ as a mediator of ischemic preconditioning. Circ Res 1997; 80:790-4.
  • Rork TH, Wallace KL, Kennedy DP, Marshall MA, Lankford AR, Linden J. Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation. Am J Physiol Heart Circ Physiol 2008;295:H1825-33
  • Balakumar P, Singh H, Reddy K, Anand-Srivastava MB. Adenosine-A1 Receptors Activation Restores the Suppressed Cardioprotective Effects of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts. J Cardiovasc Pharmacol 2009; 54: 204-12.
  • Liu GS, Thornton J, Van Winkle DM, Stanley AM, Olsson RA, Downey JM. Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation 1991; 84: 350-6.
  • Baxter GF, Marber MS, Patel VC, Yellon DM. Adenosine receptor involvement in a delayed phose of myocardial protection 24 hours after ischemic preconditioning. Circulation 1994; 90: 2993-3000.
  • Wong J, Drake L, Sajjadi F, Fristen GS, Mullane KM, Bulloough DA. Dual activation of adenosine A1 and A3 receptors mediates preconditioning of isolated cardiac myocytes. Eur J Pharmacol 1997;320:241-8.
  • Claeys MJ, Vrints CJ, Bosmans JM, Conraads VM, Snoeck JP. Aminophylline inhibits adaptation to ischaemia during angioplasty. Role of adenosine in ischaemic preconditioning. Eur Heart J 1996;17:539-44.
  • Cleveland JC, Meldrum DR, Rowland RT, Banerjea A, Harken AH. Adenosine preconditioning of human myocardium is dependent upon the ATP-sensitive potassium channel. J Mol Cell Cardiol 1997; 29: 175-81.
  • Hausenloy DJ, Tsang A, Mocanu MM, Yellon DM. Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am J Physiol Heart Circ Physiol 2005 ; 288: 971-6.
  • Uchiyama T, Engelman RM, Maulik N, Das DK. Role of Akt signaling in mitochondrial survival pathway triggered by hypoxic preconditioning. Circulation. 2004;109:3042-9.
  • Krieg T, Qin Q, Philipp S, Alexeyev MF, Cohen MV, Downey JM. Acetylcholine and bradykinin trigger preconditioning in the heart through a pathway that includes Akt and NOS. Am J Physiol Heart Circ Physiol 2004; 287: 2606-11.
  • Tsang A, Hausenley DJ, Mocanu MM, Yellon DM. Postconditioning: a form of “modified reperfusion” protects myocardium by activating Phosphatidylinositol 3-kinase- Akt pathway. Cic Res 2004;95:230-2.
  • Yang X-M, Proctor JB, Cui L, Krieg T, Doney JM, Cohen MV. Multiple brief coronary occlusions during early reperfusion protects rabbit hearts by targeting cell signal pathways. J Am Coll 2004;44:1103-10.
  • Jiang ZS, Wen GB, Tang ZH, Srisakuldee W, Fandrich RR, Kardami E. High molecular weight FGF-2 promotes postconditioning-like cardioprotection linked to activation of the protein kinase C isoforms Akt and p70 S6 kinase. Can J Physiol Pharmacol 2009;87:798- 804.
  • Krolikowski JG, Weihrauch D, Bienengraeber M, Kersten JR, Warltier DC, Pagel PS. Role of Erk1/2, p70s6K, and eNOS in isoflurane-induced cardioprotection during early reperfusion in vivo. Can J Anaesth 2006;53:174-82.
  • Yang XM, Downey JM, Cohen MV. Postconditioning’s protection is not depended on circulating blood factors or cells but requires PI3-kinase and guanyl cyclase activation. Cicrulation 2004; 110;111-68.
  • Xu Z, Yang X-M, Cohen MV, Neumann T, Heush G, Downey JM. Limitation of infarct size in rabbit hearts by the novel adenosine receptor agonist AMP 579 administrted at reperfusion. J Moll Cell Cardiol 2000;32:2339-47.
  • Yang X-M, Krieg T,Cui L, Downey JM, Cohen MV. NECA and bradykinin reperfusion reduce infarction in rabbit hearts by signaling hrough PI3K, ERK and NO. J Moll Cell Cardiol 2004;36:411-21.
  • Danielisová V, Gottlieb M, Némethová M, Burda J. Effects of bradykinin postconditioning on endogenous antioxidant enzyme activity after transient forebrain ischemia in rat. Neurochem Res 2008;33:1057-64.
  • Jonassen AK, Sack MN, Mjos OD, Yellon DM. Myocardial protectionby insulin requires early administration and is mediated via Akt and p70S6 kinase cell-survival signaling. Circ Res 2001;89:1191-8.
  • Gross ER, Hsu AK, Gross GJ. Opioid induced cardioprotection occurs via glycogen synthase kinase beta inhibition during reperfusion in intact rat hearts. Circ Res 2004;94:960-6.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Derlemeler
Yazarlar

İlker Şengül

Demet Şengül

Yayımlanma Tarihi 11 Mart 2010
Yayımlandığı Sayı Yıl 2010Cilt: 32 Sayı: 1

Kaynak Göster

AMA Şengül İ, Şengül D. İskemik ön koşullanma ve sonradan koşullanma mekanizmaları olarak intraselüler sinyalizasyon ve adenozin. CMJ. Mart 2010;32(1):127-131.