Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]

yildirim, Serkan; DINCEL, Gungor Cagdas

Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]

Güngör Çağdaş DİNÇEL, (Gümüşhane Üniversitesi, Siran Mustafa Beyaz Meslek Yüksekokulu, Laboratuvar ve Veterinerlik Sağlık Programı, Gümüşhane, Türkiye)

Serkan YILDIRIM (Atatürk Üniversitesi, Veteriner Fakültesi, Patoloji Anabilim Dalı, Erzurum, Türkiye)

Kafkas Üniversitesi Veteriner Fakültesi Dergisi

14 7

Yıl: 2016 Cilt: 22 Sayı: 3 Sayfa Aralığı: 381 - 390 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]

Öz:

Diyabetik nefropatilerin patogenezi uzun yıllardır çalışılan fakat hala tam açıklığa kavuşmuş bir konu değildir. Bu çalışma streptozotocin (STZ) ile tetiklenmiş diyabetik sıçanlarda nitrik oksit (NO) üretiminin ve oksidatif stresin (OS) nefropatoloji/nefrodejenerasyonların üzerine olan etkilerinin ve bu faktörlerin apoptozisle bir ilişkisinin olup olmadığının araştırılması için tasarlanmıştır. Bu çalışmada kaspaz 3, kaspaz 9, endotelyal nitrik oksit sentaz (eNOS), indüklenebilir nitrik oksit sentaz (iNOS) ve 8-hydroxy-2'-deoxyguanosine (8-OHdG) sunumları diyabetik böbrek dokularında araştırıldı. Çalışma sonuçlarında, 8-OHdG (P<0.005), eNOS (P<0.005), iNOS (P<0.005), kaspaz 3 (P<0.005) and kaspaz 9 (P<0.005) sunumlarının diyabetik böbrek dokularında önemli düzeyde arttığı görüldü. Bununla beraber diyabetik hayvanlarda kilo kaybı ve böbrek boyutlarında artış tespit edildi. Bu çalışmada elde edilen bulgulara göre OS ve yükselmiş NO seviyelerinin diyabetik nefropatilerin patogenezinde önemli bir rolünün olduğu düşünülmektedir. Ayrıca, STZ ile tetiklenen apoptozisin iç yolakla gerçekleştiği ve yüksek düzeyde üretilen NO'nun apoptozis düzeyini arttırdığı düşünülmektedir. Bununla beraber NO düzeylerinin artışına sadece eNOS değil iNOS'un da önemli katkı sağladığı görülmektedir. Erken diyabetik nefropatilerde NO'nun hiperfiltrasyona ve mikroalbuminüriye katkı sağladığı düşünülmektedir. 8-OHdG'nin tanısal bir öneminin olduğu ve hastalığın takibinde fikir vereceği düşünülmektedir. Sonuç olarak, diyabetik sıçan modellerinde eNOS ve iNOS'un aşırı salınımlarının apoptozisi tetikleyerek diyabetik nefropatilere neden olduğu düşünülmektedir.

Anahtar Kelime:

Konular: Veterinerlik

Streptozotosin Kaynaklı Tip 1 Diyabetik Sıçanlarda Meydana Gelen Nefropatilerde Artan eNOS ve iNOS Sunumlarının Apoptozisle İlişkilendirilmesi

Öz:

The present study was designed to evaluate the effects of high level of nitric oxide (NO) production and oxidative stress (OS) on nephropathology and to identify whether NO and OS have any correlation with apoptosis seen in diabetic kidney, elucidating the underlying mechanism(s) involved in the development of nephropathology in streptozotocin (STZ)-induced diabetic rats. Expression levels of caspase 3, caspase 9, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), for the detection of oxidative damage to DNA, were examined in diabetic kidney tissues. Results of the study revealed that the levels of 8-OHdG (P<0.005), eNOS (P<0.005), iNOS (P<0.005), caspase 3 (P<0.005) and caspase 9 (P<0.005) were remarkably higher in diabetic kidney tissues than in controls. In addition, STZ-treated animals showed significant loss of body weight and renal enlargement. It was suggested that apoptosis, OS and increased NO levels are involved in the pathogenesis of diabetic nephropathy. The results also strongly suggested that STZ-induced apoptosis through activation of the intrinsic pathway and that might be most likely related to increased NO levels. Moreover, high NO production was not only mediated by eNOS but also by iNOS. Increased NO production may contribute to hyperfiltration and microalbuminuria in early diabetic nephropathy. Furthermore, expression of 8-OHdG might give an idea of the progress and may be essential as it has a diagnostic significance for this disease. In conclusion, we believe that eNOS and iNOS overexpressions induce diabetic nephropathy by mediating apoptosis in STZ-induced rats.

Anahtar Kelime:

Konular: Veterinerlik

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

Kanwar YS, Wada J, Sun L, Xie P, Wallner EI, Chen S, Chugh S, Danesh FR: Diabetic nephropathy: Mechanisms of renal disease progression. Exp Biol Med, 233, 4-11, 2008. DOI: 10.3181/0705-MR-134
Dronavalli S, Duka I, Bakris GL: The pathogenesis of diabetic nephropathy. Nat Clin Pract Endocrinol Metab, 4, 444-452, 2008. DOI: 1038/ncpendmet0894
Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol, 35, 495-516, 2007. DOI: 10.1080/01926230701320337
Rowinsky EK: Targeted induction of apoptosis in cancer management: the emerging role of tumor necrosis factor-related apoptosis-inducing ligand receptor activating agents. J Clin Oncol, 23, 9394-9407, 2005. DOI: 1200/JCO.2005.02.2889
Loreto C, Almeida LE, Trevilatto P, Leonardi R: Apoptosis in displaced temporomandibular joint disc with and without reduction: An immunohistochemical study. J Oral Pathol Med, 40, 103-110, 2011. DOI: 10.1111/j.1600-0714.2010.00920.x
Caltabiano R, Leonardi R, Musumeci G Bartolonid G, Rusue MC, Almeidaf LE, Loretoc C: Apoptosis in temporomandibular joint disc with internal derangement involves mitochondrialdependent pathways: An in vivo study. Acta Odontol Scand, 71, 577-583, 2013. DOI: 10.3109/ 2012.700060
Roos WP, Kaina B: DNA damage-induced cell death by apoptosis. Trends Mol Med, 12, 440-450, 2006. DOI: 10.1016/j.molmed.2006.07.007
Verzola D, Bertolotto MB, Villaggio B, Ottonello L, Dallegri F, Salvatore F, Berruti V, Gandolfo MT, Garibotto G, Deferrari G: Oxidative stress mediates apoptotic changes induced by hyperglycemia in human tubular kidney cells. J Am Soc Nephrol, 15, 85-87, 2004. DOI: 1097/01.ASN.0000093370.20008.BC
Hibbs JBJ, Taintor RR, Vavrin Z: Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science, 235, 476, 1987. DOI: 10.1126/science.2432665
Bonfoco E, Krainc D, Ankarcrona M, Nicotera P, Lipton SA: Apoptosis and necrosis: Two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA, 92, 7162-7166, 1995.
Dincel GC, Kul O: eNOS and iNOS trigger apoptosis in the brains of sheep and goats naturally infected with the border disease virus. Histol Histopathol, 10, 1233-1242, 2015. DOI: 10.14670/HH-11-621
Brookes PS, Salinas EP, Darley-Usmar, Anderson PG: Concentration dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release. J Biol Chem, 275, 20474-20479, 2000. DOI: 10.1074/jbc.M001077200
Moriya R, Uehara T, Nomura Y: Mechanism of nitric oxideinduced apoptosis in human neuroblastoma SH-SY5Y cells. FEBS Lett, 484, 253- , 2000. DOI: 10.1016/S0014-5793(00)02167-0
Dincel GC, Kul O: Increased expressions of ADAMTS-13, neuronal nitric oxide synthase, and neurofilament correlate with severity of neuropathology in border disease virus-infected small ruminants. PLoS One, 10, e0120005, 2015. DOI: 10.1371/journal.pone.0120005
Dincel GC, Atmaca HT: Nitric oxide production increases during Toxoplasma gondii encephalitis in mice. Exp Parasitol, 156, 104-112, 2015. DOI: 10.1016/j.exppara.2015.06.009
Natalie JT, Hajime H, Bronk S, Gores GJ: Nitric oxide inhibits apoptosis downstream of cytochrome c release by nitrosylating caspase Cancer Res, 62, 1648-1653, 2002.
Pender MP, Rist JM: Apoptosis of inflammatory cells in immune control of the nervous system: Role of glia. Glia, 36, 137-144, 2001. DOI: 1002/glia.1103
Brown GC. Nitric oxide and neuronal death. Nitric Oxide, 23, 153-165, DOI: 10.1016/j.niox.2010.06.001
Baylis C, Harton P, Engels K: Endothelial derived relaxing factor controls renal hemodynamics in the normal rat kidney. J Am Soc Nephrol, , 875-881, 1990.
Haynes WG, Noon JP, Walker BR, Webb DJ: Inhibition of nitric oxide synthesis increases blood pressure in healthy humans. J Hypertens, 11, 1380, 1993. DOI: 10.1113/jphysiol.2009.177204
Bech JN, Nielsen CB, Pedersen EB: Effects of systemic NO synthesis inhibition on RPF, GFR, Una and vasoactive hormones in healthy humans. Am J Physiol Lung Cell Mol Physiol, 270, 845-851, 1996. DOI: 10.14814/ phy2.12144
Corson MA, James NL, Latta SE, Nerem RM, Berk BC, Harrison Classification Tree Method for ... DG: Phosphorylation of endothelial nitric oxide synthasein response to fluid shear stress. Circ Res, 79, 984-991, 1996. DOI: 10.1161/01. RES.79.5.984
Kemeny SF, Figueroa DS, Clyne AM: Hypo- and hyperglycemia impairendothelial cell actin alignment and nitricoxide synthase activation in response shear stress. PLoS One, 8, e66176, 2013. DOI: 10.1371/journal. pone.0066176
Rouhanizadeh M, Takabe W, Ai L, Yu H, Hsiai T: Monitoring oxidative stress in vascular endothelial cells in response to fluid shear stress: From biochemical analyses to micro- and nanotechnologies. Methods Enzymol, , 111-150, 2008. DOI: 10.1016/S0076-6879(08)01207-X
Edirisinghe I, Rahman I: Cigarette smoke-mediated oxidative stress, shear stress, and endothelial dysfunction: Role of VEGFR2. Ann N Y Acad Sci, 1203, 66-72, 2010. DOI: 10.1111/j.1749-6632.2010.05601.x

APA	DINCEL G, yildirim S (2016). Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. , 381 - 390.
Chicago	DINCEL Gungor Cagdas,yildirim Serkan Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. (2016): 381 - 390.
MLA	DINCEL Gungor Cagdas,yildirim Serkan Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. , 2016, ss.381 - 390.
AMA	DINCEL G,yildirim S Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. . 2016; 381 - 390.
Vancouver	DINCEL G,yildirim S Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. . 2016; 381 - 390.
IEEE	DINCEL G,yildirim S "Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]." , ss.381 - 390, 2016.
ISNAD	DINCEL, Gungor Cagdas - yildirim, Serkan. "Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]". (2016), 381-390.

APA	DINCEL G, yildirim S (2016). Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 22(3), 381 - 390.
Chicago	DINCEL Gungor Cagdas,yildirim Serkan Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. Kafkas Üniversitesi Veteriner Fakültesi Dergisi 22, no.3 (2016): 381 - 390.
MLA	DINCEL Gungor Cagdas,yildirim Serkan Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, vol.22, no.3, 2016, ss.381 - 390.
AMA	DINCEL G,yildirim S Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 2016; 22(3): 381 - 390.
Vancouver	DINCEL G,yildirim S Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 2016; 22(3): 381 - 390.
IEEE	DINCEL G,yildirim S "Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]." Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 22, ss.381 - 390, 2016.
ISNAD	DINCEL, Gungor Cagdas - yildirim, Serkan. "Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats [1] [2]". Kafkas Üniversitesi Veteriner Fakültesi Dergisi 22/3 (2016), 381-390.