Post-Translational Modification of Manganese Superoxide Dismutase in Acutely Rejecting Cardiac Transplants: Role of Inducible Nitric Oxide Synthase

Nilakantan, Vani; Halligan, Nadine; Nguyen, Thanh Kim; Hilton, Gail; Khanna, Ashwani; Roza, Allan M.; Johnson, Christopher P.; Adams, Mark B.; Pieper, Galen M.

doi:10.1016/j.healun.2005.01.009

Cited by 41 publications

(39 citation statements)

References 27 publications

(40 reference statements)

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“…This concept would be consistent with our earlier findings that protein nitration is increased at post-transplant day 6 [89] when cardiac NO content is decreased but nitration is not increased at post-transplant day 4 when cardiac NO content is elevated in cardiac allografts.…”

Section: Post-translational Regulation Of No Bioactivity From Inossupporting

confidence: 92%

“…The theory here is that the former scavenges NO while the latter inhibits iNOS up-regulation. Additional studies in our laboratory using L-NIL show that this treatment blocked the increase in total protein nitration within the graft without altering iNOS expression, thereby, implicating a role of iNOSderived protein nitration presumably [89]. This finding agreed with previous studies showing inhibition of nitration using other selective iNOS inhibitors [64,127].…”

Section: Pathways Of Protein Nitration In Cardiac Rejectionsupporting

confidence: 88%

“…Here again, the inhibition of aconitase enzymatic activity in acute cardiac allograft rejection was prevented by both cyclosporine or L-NIL treatments. This inactivation preceeded the nitration of MnSOD reported elsewhere [89]. Since most all of the aconitase activity in heart is mitochondrial in origin, it is intriguing to speculate that mitochondrial aconitase inactivation could provide, at least in part, a source of reactive oxygen for mitochondrial protein nitration.…”

Section: Limitationsmentioning

confidence: 77%

“…Nitration of specific proteins such as the mitochondrial proteins MnSOD or cytochrome c has been demonstrated in both renal and cardiac allograft rejection [89,123]. Collectively, nitration of these proteins may be a mechanism to signal a cascade of events leading to apoptosis.…”

Section: Peroxynitrite and Protein Nitration In Cardiac Allograft Rejmentioning

confidence: 99%

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The complex role of iNOS in acutely rejecting cardiac transplants

Pieper

Roza

2008

Free Radical Biology and Medicine

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This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutelyrejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed.

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Section: Post-translational Regulation Of No Bioactivity From Inossupporting

confidence: 92%

Section: Pathways Of Protein Nitration In Cardiac Rejectionsupporting

confidence: 88%

Section: Limitationsmentioning

confidence: 77%

Section: Peroxynitrite and Protein Nitration In Cardiac Allograft Rejmentioning

confidence: 99%

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The complex role of iNOS in acutely rejecting cardiac transplants

Pieper

Roza

2008

Free Radical Biology and Medicine

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“…Given that CSIS exhibited CORT levels similar to basal values, in the current study a state of oxidative stress may have resulted from overexpression of both nNOS and iNOS, which has previously been shown as a hallmark of nitrosative stress in the brain during chronic stress . In addition, overexpressed NO may act with superoxide anion and lead to the formation of peroxynitrite that may inactivate MnSOD via nitration causing a decrease in either its activity or protein levels (Nilakantan et al, 2005). The reduced CuZnSOD activity could be a consequence of high levels of superoxide anion produced during oxidative stress, which undergoes dismutation to form elevated levels of hydrogen peroxide.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of regulation of antioxidant enzymes in the brain and liver of acutely and/or chronically stressed rats

Zlatković¹

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Najveću zahvalnost dugujem upravo mom mentoru, dr Dragani Filipović, koja me je uvela u metode naučnog rada i tokom godina usmeravala u profesionalnom razvoju. Hvala na prenetom znanju, stručnom vođenju, kao i na svim sugestijama i smernicama koje su me formirale kao istraživača.Veliko hvala za svo utrošeno vreme, savete i konstruktivne kritike koje su dovele do krajnjeg oblikovanja ove teze. Dr Nadeždi Nedeljković se zahvaljujem na ukazanom poverenju i korisnim savetima tokom doktorskih studija.Dr Siniši Đuraševiću se zahvaljujem na savetima i pomoći oko interpretacije pojedinih rezultata. Dr Snežani Pajović veliko hvala na omogućenim uslovima za eksperimentalni rad.Neizmerno hvala porodici i prijateljima, na svemu kroz šta su prošli zajedno sa mnom, na ljubavi i smehu, čineći da sve, pa i ova disertacija, dobije sasvim novu dimenziju. . REZIME Molekularni mehanizmi regulacije antioksidativnih enzima u mozgu i jetri akutno i/ili hronično stresiranih pacovaAktivacija hipolamo-hipofizo-adrenalne (HHA) ose predstavlja jedan od odgovora organizma na izlaganje stresnim uslovima. Dok aktivacija HHA ose uzrokovana kratkotrajnim stresorima ima adaptivni karakter, hroničan stres može dovesti do brojnih patoloških promena među kojima su i poremećaji raspoloženja. Uzrok deregulacije HHA ose u stresnim uslovima još uvek nije u potpunosti utvrđen, a smatra se da može biti povezan sa i pojavom oksidativnog stresa. Stoga je ispitana i okarakterisana aktivnost HHA ose, merenjem koncentracije kortikosterona (CORT) kao markera stresnog odgovora, kao i mehanizmi regulacije antioksidativnih enzima CuZnSOD iMnSOD, kao biomarkera oksidativnog stresa, u uslovima akutnog, hroničnog i kombinovanog stresa u hipokampusu i prečeonoj kori mozga i jetri mužjaka pacova Wistar soja. Cilj ove teze je bio bolje razumevanje biohemijskih i molekularnih mehanizama delovanja antioksidativnih enzima u moždanim strukturama i jetri pacova nakon izlaganja 21-dnevnoj socijalnoj izolaciji, koja predstavlja jedan od životinjskih modela depresije. Akutno izlaganje imobilizaciji ili niskoj temperaturi u trajanju od 2 sata korišćeno je kao pokazatelj "normalnog" odgovora na stres, dok je kombinacija hroničnog i akutnog stresa služila kao potvrda maladaptivnog efekta hroničnog stresa.Rezultati istraživanja su pokazali povećanu koncentraciju CORT-a u serumu životinja izloženih akutnim stresorima, dok su kod životinja izlaganih hroničnoj socijalnoj izolaciji vrednosti ostale nepromenjene. Međutim, značajno niža koncentracija CORT-a između životinja koje su izlagane kombinovanom i odgovarajućem akutnom stresu ukazala je na poremećaj u regulaciji HHA ose koji je izazvana hroničnom socijalnom izolacijom, a što je rezultovalo u neadekvatnm odgovoru na nove stresne situacije.Akutni stres imobilizacije doveo je do povećanja ekspresije MnSOD proteina u mitohondrijama obe moždane strukture, dok je kod životinja akutno izlaganih niskoj temperaturi ili hroničnom stresu izolacije nivo ovog proteina ostao nepromenjen. Međutim, aktivnostiCuZnSOD i MnSOD-a u prečeonoj kori n...

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Oxidative Stress in Cardiac Transplantation

Pieper

Khanna

2010

Studies on Cardiovascular Disorders

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Post-Translational Modification of Manganese Superoxide Dismutase in Acutely Rejecting Cardiac Transplants: Role of Inducible Nitric Oxide Synthase

Cited by 41 publications

References 27 publications

The complex role of iNOS in acutely rejecting cardiac transplants

The complex role of iNOS in acutely rejecting cardiac transplants

Molecular mechanisms of regulation of antioxidant enzymes in the brain and liver of acutely and/or chronically stressed rats

Oxidative Stress in Cardiac Transplantation

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