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Rolipram rescues oxidative stress‐induced premature phenotypes by SIRT6‐dependent NF‐kappaB inhibition (1142.11)
Author(s) -
Wang Zhao,
Liang Yaru
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1142.11
Subject(s) - rolipram , sirtuin , sirt2 , sirt6 , cyclic adenosine monophosphate , oxidative stress , endocrinology , sirtuin 1 , medicine , phenotype , resveratrol , phosphodiesterase , chemistry , pharmacology , biology , enzyme , nad+ kinase , downregulation and upregulation , biochemistry , gene , receptor
Cyclic adenosine monophosphate (cyclic AMP) is a key mediator of metabolic regulation and its signalling pathway is highly complex. Recent studies showed that resveratrol activates SIRT1 by increasing cyclic AMP signalling pathway to ameliorate aging‐related metabolic phenotypes. However, whether cyclic AMP itself could also rescue aging‐related functional declines remains unknown. We suppose that cyclic AMP may also contribute to other Sirtuin family members. We investigated the physiological and metabolic changes in oxidative stress‐induced premature mice, which were treated with experimental galactosemia and developed glycometabolism dysfunction. Here, we demonstrated that Rolipram, the specific PDE4 inhibitor, could increase cyclic AMP level to rescue the pathophysiology in premature mice. The mice treated with Rolipram showed increased SIRT6 and reduced acetylated NF‐kappaB protein level. However, cyclic AMP lost its inhibition effect on NF‐kappaB when SIRT6 was knocked down. Therefore, administration of Rolipram may protect against premature phenotypes in galactosemia or other glycometabolism dysfunction.