Oxidative mechanisms in diabetes related urinary bladder dysfunction
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The Ohio State University / OhioLINK
2003
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1060880772 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu10608807722021-08-03T05:48:09Z Oxidative mechanisms in diabetes related urinary bladder dysfunction Pitre, Deepali urinary bladder diabetes oxidative stress Rac1 remodeling Urinary bladder dysfunction is a common complication with diabetes and is associated with several debilitating symptoms. While the phenomenon is well recognized, its pathogenesis is not well understood and hence, improved mechanistic understanding is necessary for advancement of improved therapies. Using the well-recognized streptozotocin induced diabetic rat model, we observed time dependent and regionally distinct early biochemical changes after the induction of diabetes that likely include increased NO signaling and protein tyrosine nitration. As these changes precede measures of significant modeling, it is likely that such NO signaling is involved in the process of remodeling. Furthermore, automated digital imaging technologies provide a reproducible and convenient method for detailed morphometric analysis of bladder tissues. We then downsized our techniques to study bladder morphology and function from rat to mouse model. We observed functional, structural and neuronal remodeling at 5 weeks. Later biochemical changes after the induction of diabetes (occurring after substantial remodeling is documented) suggest involvement of Rac1 and MAPK mediated signaling in either regulation or maintenance of remodeling. The changes that occur suggest that oxidative signaling pathways may be involved and that, especially in urothelium, signaling pathways having many elements in common with induction of inflammatory events are involved (even though there is no evidence for typical inflammatory responses). In an effort to investigate the consequences of Rac1 induction with respect to bladder function and structure, we employed a transgenic mouse model of Rac1 constitutively over expressed via selective smooth muscle promoter. We investigated the role of oxidative stress alone as an important participant in altering the bladder, in absence of diabetes (e.g. absence of increased glucose or volume related changes). The Rac1 overexpression mouse model in which remodeling occurs in the absence of volume changes, making this the first model for studying non-volume induced remodeling. Rac1 overexpression mouse model confirms that substantial bladder remodeling occurs in response to increased activity of Rac1 and MAPK mediated signaling, independently of changes in volume of urine. Further investigations may provide new insight regarding adaptive and maladaptive processes in bladder physiology and enhanced opportunities for improved therapeutic strategies for an important diabetic complication. 2003 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1060880772 http://rave.ohiolink.edu/etdc/view?acc_num=osu1060880772 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
urinary bladder diabetes oxidative stress Rac1 remodeling |
| spellingShingle |
urinary bladder diabetes oxidative stress Rac1 remodeling Pitre, Deepali Oxidative mechanisms in diabetes related urinary bladder dysfunction |
| author |
Pitre, Deepali |
| author_facet |
Pitre, Deepali |
| author_sort |
Pitre, Deepali |
| title |
Oxidative mechanisms in diabetes related urinary bladder dysfunction |
| title_short |
Oxidative mechanisms in diabetes related urinary bladder dysfunction |
| title_full |
Oxidative mechanisms in diabetes related urinary bladder dysfunction |
| title_fullStr |
Oxidative mechanisms in diabetes related urinary bladder dysfunction |
| title_full_unstemmed |
Oxidative mechanisms in diabetes related urinary bladder dysfunction |
| title_sort |
oxidative mechanisms in diabetes related urinary bladder dysfunction |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2003 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1060880772 |
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AT pitredeepali oxidativemechanismsindiabetesrelatedurinarybladderdysfunction |
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