Unilateral ureteral obstruction induces DNA repair by APE1

Maria Diget Aamann; Rikke Norregaard; Marie Louise V Kristensen; Tinna Stevnsner; Jørgen Frøkiær

doi:10.1152/ajprenal.00613.2014

Unilateral ureteral obstruction induces DNA repair by APE1

Maria Diget Aamann, Rikke Norregaard, Marie Louise V Kristensen, Tinna Stevnsner, Jørgen Frøkiær

Department of Clinical Medicine

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

4 Citations (Scopus)

Abstract

Ureteral obstruction is associated with oxidative stress and the development of fibrosis of the kidney parenchyma. Apurinic/apyrimidinic endonuclease (APE1) is an essential DNA repair enzyme for repair of oxidative DNA lesions and regulates several transcription factors. The aim of the present study was to investigate whether APE1 is regulated by acute (24 h) and chronic (7 days) unilateral ureteral obstruction (UUO). APE1 was expressed in essentially all kidney cells with the strongest expression in proximal tubuli. After 24 h of UUO, APE1 mRNA was induced in the cortex, inner stripe of the outer medulla (ISOM), and inner medulla (IM). In contrast, the APE1 protein level was not regulated in the IM and ISOM and only slightly increased in the cortex. APE1 DNA repair activity was not significantly changed. A different pattern of regulation was observed after 7 days of UUO, with an increase of the APE1 mRNA level in the cortex but not in the ISOM and IM. The APE1 protein level in the cortex, ISOM, and IM increased significantly. Importantly, we observed a significant increase in APE1 DNA repair activity in the cortex and IM. To confirm our model, we investigated heme oxygenase-1, collagen type I, fibronectin I, and α-smooth muscle actin levels. In vitro, we found the transcriptional regulatory activity of APE1 to be involved in the upregulation of the profibrotic factor connective tissue growth factor. In summary, APE1 is regulated at different levels after acute and chronic UUO. Thus, our results suggest that DNA repair activity is regulated in response to progressive (7 days) obstruction and that APE1 potentially could play a role in the development of fibrosis in kidney disease.

Original language	English
Journal	American Journal of Physiology: Renal Physiology
Volume	310
Issue	8
Pages (from-to)	F763-F776
Number of pages	14
ISSN	1931-857X
DOIs	https://doi.org/10.1152/ajprenal.00613.2014
Publication status	Published - 2016

Keywords

Apurinic/apyrimidinic endonuclease I
DNA repair
Fibrosis
Kidney
Obstructive nephropathy
Unilateral ureteral obstruction

Access to Document

10.1152/ajprenal.00613.2014

Cite this

@article{6f78e32dd0794346b9198aec0a044e6c,

title = "Unilateral ureteral obstruction induces DNA repair by APE1",

abstract = "Ureteral obstruction is associated with oxidative stress and the development of fibrosis of the kidney parenchyma. Apurinic/apyrimidinic endonuclease (APE1) is an essential DNA repair enzyme for repair of oxidative DNA lesions and regulates several transcription factors. The aim of the present study was to investigate whether APE1 is regulated by acute (24 h) and chronic (7 days) unilateral ureteral obstruction (UUO). APE1 was expressed in essentially all kidney cells with the strongest expression in proximal tubuli. After 24 h of UUO, APE1 mRNA was induced in the cortex, inner stripe of the outer medulla (ISOM), and inner medulla (IM). In contrast, the APE1 protein level was not regulated in the IM and ISOM and only slightly increased in the cortex. APE1 DNA repair activity was not significantly changed. A different pattern of regulation was observed after 7 days of UUO, with an increase of the APE1 mRNA level in the cortex but not in the ISOM and IM. The APE1 protein level in the cortex, ISOM, and IM increased significantly. Importantly, we observed a significant increase in APE1 DNA repair activity in the cortex and IM. To confirm our model, we investigated heme oxygenase-1, collagen type I, fibronectin I, and α-smooth muscle actin levels. In vitro, we found the transcriptional regulatory activity of APE1 to be involved in the upregulation of the profibrotic factor connective tissue growth factor. In summary, APE1 is regulated at different levels after acute and chronic UUO. Thus, our results suggest that DNA repair activity is regulated in response to progressive (7 days) obstruction and that APE1 potentially could play a role in the development of fibrosis in kidney disease.",

keywords = "Apurinic/apyrimidinic endonuclease I, DNA repair, Fibrosis, Kidney, Obstructive nephropathy, Unilateral ureteral obstruction",

author = "Aamann, {Maria Diget} and Rikke Norregaard and Kristensen, {Marie Louise V} and Tinna Stevnsner and J{\o}rgen Fr{\o}ki{\ae}r",

note = "Copyright {\textcopyright} 2014, American Journal of Physiology - Renal Physiology.",

year = "2016",

doi = "10.1152/ajprenal.00613.2014",

language = "English",

volume = "310",

pages = "F763--F776",

journal = "American Journal of Physiology: Renal Physiology",

issn = "1931-857X",

publisher = "American Physiological Society",

number = "8",

}

Unilateral ureteral obstruction induces DNA repair by APE1. / Aamann, Maria Diget; Norregaard, Rikke; Kristensen, Marie Louise V et al.
In: American Journal of Physiology: Renal Physiology, Vol. 310, No. 8, 2016, p. F763-F776.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Unilateral ureteral obstruction induces DNA repair by APE1

AU - Aamann, Maria Diget

AU - Norregaard, Rikke

AU - Kristensen, Marie Louise V

AU - Stevnsner, Tinna

AU - Frøkiær, Jørgen

PY - 2016

Y1 - 2016

N2 - Ureteral obstruction is associated with oxidative stress and the development of fibrosis of the kidney parenchyma. Apurinic/apyrimidinic endonuclease (APE1) is an essential DNA repair enzyme for repair of oxidative DNA lesions and regulates several transcription factors. The aim of the present study was to investigate whether APE1 is regulated by acute (24 h) and chronic (7 days) unilateral ureteral obstruction (UUO). APE1 was expressed in essentially all kidney cells with the strongest expression in proximal tubuli. After 24 h of UUO, APE1 mRNA was induced in the cortex, inner stripe of the outer medulla (ISOM), and inner medulla (IM). In contrast, the APE1 protein level was not regulated in the IM and ISOM and only slightly increased in the cortex. APE1 DNA repair activity was not significantly changed. A different pattern of regulation was observed after 7 days of UUO, with an increase of the APE1 mRNA level in the cortex but not in the ISOM and IM. The APE1 protein level in the cortex, ISOM, and IM increased significantly. Importantly, we observed a significant increase in APE1 DNA repair activity in the cortex and IM. To confirm our model, we investigated heme oxygenase-1, collagen type I, fibronectin I, and α-smooth muscle actin levels. In vitro, we found the transcriptional regulatory activity of APE1 to be involved in the upregulation of the profibrotic factor connective tissue growth factor. In summary, APE1 is regulated at different levels after acute and chronic UUO. Thus, our results suggest that DNA repair activity is regulated in response to progressive (7 days) obstruction and that APE1 potentially could play a role in the development of fibrosis in kidney disease.

AB - Ureteral obstruction is associated with oxidative stress and the development of fibrosis of the kidney parenchyma. Apurinic/apyrimidinic endonuclease (APE1) is an essential DNA repair enzyme for repair of oxidative DNA lesions and regulates several transcription factors. The aim of the present study was to investigate whether APE1 is regulated by acute (24 h) and chronic (7 days) unilateral ureteral obstruction (UUO). APE1 was expressed in essentially all kidney cells with the strongest expression in proximal tubuli. After 24 h of UUO, APE1 mRNA was induced in the cortex, inner stripe of the outer medulla (ISOM), and inner medulla (IM). In contrast, the APE1 protein level was not regulated in the IM and ISOM and only slightly increased in the cortex. APE1 DNA repair activity was not significantly changed. A different pattern of regulation was observed after 7 days of UUO, with an increase of the APE1 mRNA level in the cortex but not in the ISOM and IM. The APE1 protein level in the cortex, ISOM, and IM increased significantly. Importantly, we observed a significant increase in APE1 DNA repair activity in the cortex and IM. To confirm our model, we investigated heme oxygenase-1, collagen type I, fibronectin I, and α-smooth muscle actin levels. In vitro, we found the transcriptional regulatory activity of APE1 to be involved in the upregulation of the profibrotic factor connective tissue growth factor. In summary, APE1 is regulated at different levels after acute and chronic UUO. Thus, our results suggest that DNA repair activity is regulated in response to progressive (7 days) obstruction and that APE1 potentially could play a role in the development of fibrosis in kidney disease.

KW - Apurinic/apyrimidinic endonuclease I

KW - DNA repair

KW - Fibrosis

KW - Kidney

KW - Obstructive nephropathy

KW - Unilateral ureteral obstruction

UR - http://www.scopus.com/inward/record.url?scp=84983749139&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00613.2014

DO - 10.1152/ajprenal.00613.2014

M3 - Journal article

C2 - 26608791

SN - 1931-857X

VL - 310

SP - F763-F776

JO - American Journal of Physiology: Renal Physiology

JF - American Journal of Physiology: Renal Physiology

IS - 8

ER -

Unilateral ureteral obstruction induces DNA repair by APE1

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this