During mammary gland involution, different signals are required for apoptosis and tissue remodelling. To explore the role of NO in the involution of mammary tissue after lactation, NOS2 (inducible nitric oxide synthase)-KO (knockout) mice were used. No apparent differences were observed between NOS2-KO and WT (wild-type) animals during pregnancy and lactation. However, upon cessation of lactation, a notable delay in involution was observed, compared with WT mice. NOS2-KO mice showed increased phosphorylation of STAT (signal transducer and activator of transcription) 5 during weaning, concomitant with increased β-casein mRNA levels when compared with weaned WT glands, both hallmarks of the lactating period. In contrast, activation of STAT3, although maximal at 24 h after weaning, was significantly reduced in NOS2-KO mice. STAT3 and NF-κB (nuclear factor κB) signalling pathways are known to be crucial in the regulation of cell death and tissue remodelling during involution. Indeed, activation of both STAT3 and NF-κB was observed in WT mice during weaning, concomitant with an increased apoptotic rate. During the same period, less apoptosis, in terms of caspase 3 activity, was found in NOS2-KO mice and NF-κB activity was significantly reduced when compared with WT mice. Furthermore, the activation of the NF-κB signalling pathway is delayed in NOS2-KO mice when compared with WT mice. These results emphasize the role of NO in the fine regulation of the weaning process, since, in the absence of NOS2, the switching on of the cascades that trigger involution is hindered for a time, retarding apoptosis of the epithelial cells and extracellular matrix remodelling.
Skip Nav Destination
Article navigation
June 2010
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
May 27 2010
Nitric oxide triggers mammary gland involution after weaning: remodelling is delayed but not impaired in mice lacking inducible nitric oxide synthase
Rosa Zaragozá;
Rosa Zaragozá
1Departamento de Bioquímica y Biología Molecular/Fundación Investigación Hospital Clínico Valencia, Facultad de Medicina, Universidad de Valencia, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain
Search for other works by this author on:
Ana Bosch;
Ana Bosch
1Departamento de Bioquímica y Biología Molecular/Fundación Investigación Hospital Clínico Valencia, Facultad de Medicina, Universidad de Valencia, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain
Search for other works by this author on:
Concha García;
Concha García
1Departamento de Bioquímica y Biología Molecular/Fundación Investigación Hospital Clínico Valencia, Facultad de Medicina, Universidad de Valencia, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain
Search for other works by this author on:
Juan Sandoval;
Juan Sandoval
1Departamento de Bioquímica y Biología Molecular/Fundación Investigación Hospital Clínico Valencia, Facultad de Medicina, Universidad de Valencia, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain
Search for other works by this author on:
Eva Serna;
Eva Serna
1Departamento de Bioquímica y Biología Molecular/Fundación Investigación Hospital Clínico Valencia, Facultad de Medicina, Universidad de Valencia, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain
Search for other works by this author on:
Luís Torres;
Luís Torres
1Departamento de Bioquímica y Biología Molecular/Fundación Investigación Hospital Clínico Valencia, Facultad de Medicina, Universidad de Valencia, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain
Search for other works by this author on:
Elena R. García-Trevijano;
Elena R. García-Trevijano
1Departamento de Bioquímica y Biología Molecular/Fundación Investigación Hospital Clínico Valencia, Facultad de Medicina, Universidad de Valencia, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain
Search for other works by this author on:
Juan R. Viña
Juan R. Viña
1
1Departamento de Bioquímica y Biología Molecular/Fundación Investigación Hospital Clínico Valencia, Facultad de Medicina, Universidad de Valencia, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain
1To whom correspondence should be addressed to (email Juan.R.Vina@uv.es).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 17 2009
Revision Received:
March 08 2010
Accepted:
March 26 2010
Accepted Manuscript online:
March 26 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 428 (3): 451–462.
Article history
Received:
July 17 2009
Revision Received:
March 08 2010
Accepted:
March 26 2010
Accepted Manuscript online:
March 26 2010
Citation
Rosa Zaragozá, Ana Bosch, Concha García, Juan Sandoval, Eva Serna, Luís Torres, Elena R. García-Trevijano, Juan R. Viña; Nitric oxide triggers mammary gland involution after weaning: remodelling is delayed but not impaired in mice lacking inducible nitric oxide synthase. Biochem J 15 June 2010; 428 (3): 451–462. doi: https://doi.org/10.1042/BJ20091091
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.