NDLI: Hyperglycemia promotes p53-Mdm2 interaction but reduces p53 ubiquitination in RINm5F cells

Content Provider	Springer Nature Link
Author	Raúl, Barzalobre Gerónimo Antonio, Flores López Luis Arturo, Baiza Gutman Luis Miguel, Cruz Rebeca, García Macedo Alejandro, Ávalos Rodríguez Alejandra, Contreras Ramos Margarita, Díaz Flores Clara, Ortega Camarillo
Copyright Year	2015
Abstract	The apoptosis of β cells induced by hyperglycemia has been associated with p53 mobilization to mitochondria and p53 phosphorylation. Murine double minute 2 (Mdm2) induces the degradation of p53 and thereby protects cells from apoptosis. We studied the effect of glucose at high concentration on the ability of Mdm2 to ubiquitinate p53 and promote its degradation. RINm5F cells were grown in RPMI-1640 medium with 5 or 30 mM glucose for varying periods of time. After this treatment, the expression of Mdm2 was measured using real-time PCR. The phosphorylation of Mdm2 at Ser166, p53 at Ser15, and the kinases Akt and ATM were measured by Western blotting. The formation of the p53-Mdm2 complex and p53 ubiquitination was assessed by p53 immunoprecipitation and immunofluorescence. Our results showed that high glucose reduced Mdm2 mRNA expression and protein concentration and increased Mdm2 and Akt phosphorylation, albeit with slower kinetics for Akt. It also promoted p53-Mdm2 complex formation, whereas p53 ubiquitination was suppressed. Furthermore, phosphorylation of both p53 Ser15 and ATM was increased in the presence of 30 mM glucose. These data indicate that high concentration glucose decrease the mRNA expression and cytosolic concentration of Mdm2. However, although the increase in glucose promoted the phosphorylation of Mdm2, it also decreased p53 ubiquitination, thus avoiding p53 degradation. In hyperglycemic conditions, such as diabetes mellitus, the reduction of pancreatic β cells mass is favored by stabilization of p53 in association with low p53 ubiquitination and reduced expression of Mdm2.
Starting Page	257
Ending Page	264
Page Count	8
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	405
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2015-04-28
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Mdm2 p53 Beta cells Ubiquitin pMdm2 Ser166 Hyperglycemia Biochemistry Medical Biochemistry Oncology Cardiology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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Erratum to: Hyperglycemia promotes p53-Mdm2 interaction but reduces p53 ubiquitination in RINm5F cells

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