Oğuzhan ÖZCAN, Hüseyin ERDAL, Gökhan ÇAKIRCA, Zafer YÖNDEN

Oksidatif stres ve hücre içi lipit, protein ve DNA yapıları üzerine etkileri

Oksidatif stres, hücresel metabolizma sırasında oluşan hidroksil radikali, süperoksit radikali ve hidrojen peroksit gibi reaktif oksijen türlerinin artışı (ROS) ile onları detoksifiye eden, antioksidanların yetersizliği sonucu oksidatif dengenin bozulması olarak tanımlanır. Oksidatif stresteki artış sonucunda oluşan reaktif oksijen türleri hücre içi lipit ve protein yapıların çift bağ içeren gruplarına ve DNA'daki bazların çift bağlarına saldırır ve bir hidrojen atomu kopararak zincirleme oksidasyon reaksiyonlarını başlatırlar. Sonuçta hücre içi lipit, protein ve DNA gibi makromoleküller hasarlanarak hücre zedelenmesi veya hücre ölümü meydana gelir. Serbest radikallerin etkileri ile makromoleküllerin oksidatif hasarı sonucunda açığa çıkan malondialdehit (MDA) , protein karbonil (PCO), 8-hidroksiguanin (8-OHG) gibi ürünlerin vücut sıvıları ve dokularda biyokimyasal yöntemlerle ölçülmesi ile oksidatif hasar varlığı tespit edilir. Son yıllarda bu alanda gittikçe artan sayıda çalışmaya rağmen halen oksidatif stresin hücre içi yapılar üzerine etkisi bütün yönleriyle bilinmemektedir. Bu derlemede oksidatif stresin oluşum mekanizması, antioksidan sistemler ve etki mekanizmaları, hücre içi yapılara olan etkileri ve oksidatif streste oluşan yıkım ürünlerinin biyokimyasal yönden değerlendirilmesi hedeflenmiştir

Oxidative stress and its impacts on intracellular lipids, proteins and DNA

Oxidative stress is described as disturbed oxidative balance between increased reactive oxygen species such as hydroxyl radical (OHo), superoxide radical (O2-), hydrogen peroxide (H2O2) which occurs during normal cellular metabolism and decreased antioxidants which have scavenging effects on free radicals. Reactive oxygen species resulted from increased oxidative stress attacks on to the double bonds of lipids, proteins and DNA bases, removing one hydrogen atom from structure and initiate to oxidative chain reactions. This process leads to cellular damage and death damaging intracellular macromolecules such as lipids, proteins and DNA. The damage of free radicals is detected measuring oxidative products such as malondialdehyde (MDA), protein carbonyl (PCO) and 8-hydroxyguanine derivatives (8-OHG, 8-hidroksi-2?deoksiguanozin) in body fluids and various tissues.Although considerable amount of studies in this field, the effects of oxidative stress on cellular structures still remain unknown. In this review, we aimed to evaluate the biochemical aspects of oxidative stress, antioxidant systems and their mechanism of actions and oxidative products.

PDF

___

Yan LJ, Sohal RS. Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci U S A 1998;95:896-901.
Yan LJ. Positive oxidative stress in aging and aging-related disease tolerance. Redox Biol 2014:9;165-169.
Dokuyucu R, Karateke A, Gokce H, et al. Antioxidant effects of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol 2014;183:23-27.
Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem. 1997;272:20313-20316.
Motor S, Ozturk S, Ozcan O, et al. Evaluation of total antioxidant status, total oxidant status and oxidative stres index in patients with alopecia areata. Int J Clin Exp Med 2014;7: 1089-1093.
Aydın M, Selcoki Y, Nazlı Y, et al. Relationship between total antioxidant capacity and the severity of coronary artery Disease. J Clin Exp Invest 2012;3:22-28.
Şahin DY, Elbasan Z, Gür M, et al. Relationship between oxidative stress markers and cardiac syndrome X. J Clin Exp Invest 2012;3:174-180.
Kılınç K, Kılınç A. Oksijen toksisitesinin aracı molekülleri olarak oksijen radikalleri. Hacettepe Tıp Dergisi 2002;33:110-118.
Navarro A, Boveris A. Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging. Am J Physiol Regul Integr Comp Physiol 2004;287:1244-1249.
Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12:1161-1208.
Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109-142.
Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology 2011;283:65-87.
Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism and signaling mechanisms of malondialdehydeand 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014;2014:360438.
Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis. Chem Rev 2011;111:5944- 5972.
Gupta RK, Patel AK, Shah N, et al. Oxidative stress and antioxidants in disease and cancer: a review. Asian Pac J Cancer Prev 2014;15:4405-4409.
Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995;41:1819-1828.
Sies H. Oxidative stress: from basic research to clinical application. Am J Med 1991;91: 31-38.
Girotti AW. Lipid hydroperoxide generation, turnover, and effector action in biological systems, J Lipid Res 1998;39:1529-1542.
Kanner J, German JB, Kinsella JE. Initiation of lipid peroxidation in biological systems. Crit Rev Food Sci Nutr 1987;25:317-364.
Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11:81-128.
Catalá A. An overview of lipid peroxidation with emphasis in outer segments of photoreceptors and the chemiluminescence assay. Int J Biochem Cell Biol 2006;38:1482-1495.
Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 1990;186:407- 421.
Pryor WA. On the detection of lipid hydroperoxides in biological samples. Free Radic Biol Med 1989;7:177- 178.
Prokai L, Yan LJ, Vera-Serrano JL, et al. Mass spectrometry-based survey of age-associated protein carbonylation in rat brain mitochondria. J Mass Spectrom 2007;42:1583-1589.
Rao RS, Moller IM. Pattern of occurrence and occupancy of carbonylation sites in proteins. Proteomics 2011;11:4166-4173
Dalle-Donne I, Rossi R, Giustarini D, et al. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 2003;329:23-38.
Levine RL, Garland D, Oliver CN, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990;186:464-478.
Breen AP and Murphy JA. Reactions of oxyl radicals with DNA. Free Radic Biol Med 1995;18:1033-1077.
Helbock HJ, Beckman KB, Ames BN. 8-Hydroxy- deoxyguanosine and 8-Hydroxy-guanine as biomarkers of oxidative DNA damage. Methods Enzymol 1999;300:156-166.
Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. Faseb J 2003;17:1195-214.
Hu JJ, Dubin N, Kurland D, Ma BL and Roush GC. The effects of hydrogen peroxide on DNA repair activities. Mutat Res 1995;336:193-201.
Hardie LJ, Briggs JA, Davidson LA, et al. The effect of hOGG1 and glutathione peroxidase I genotypes and 3p chromosomal loss on 8-hydroxydeoxyguanosine levels in lung cancer. Carcinogenesis 2000;21:167- 172.