Impaired cAMP-mediated gene expression and decreased cAMP response element binding protein in senescent cells

Chin, Jane H.; Okazaki, Masahiro; Frazier, James S.; Hu, Zhiwei; Hoffman, Brian B.

doi:10.1152/ajpcell.1996.271.1.c362

Cited by 44 publications

(13 citation statements)

References 11 publications

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“…In addition, CREB phosphorylation in crude wet samples was greater than that in purified freezedried muscle, at rest as well as during exercise. The origin of the observed CREB phosphorylation in muscle remains speculative, but may include fibroblasts [9], endothelial cells [21,31], monocytes [28] and lymphocytes [29]. As shown in the present study, the freeze-drying process itself does not change the amount of MEK1/2, ERK1/2 and CREB proteins in the phosphorylated state.…”

Section: Discussionsupporting

confidence: 54%

Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle

Widegren

Wretman

Lionikas

et al. 2000

Pfl�gers Archiv European Journal of Physiology

109

102

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The mitogen-activated protein (MAP) kinase pathways have been highlighted as a possible link between exercise and adaptive changes in skeletal muscle. In this study, the effect of exercise intensity on the activation of the ERK/MAP kinase pathway was investigated in human skeletal muscle. One-leg exercise at low (40% maximal oxygen consumption, VO2max for 30 min) and high (75% VO2max for 30 min) intensity resulted in 11.5+8. I-fold and 39.7+/-6.3-fold (mean +/-SEM) increases in ERK1/2 phosphorylation (P<0.001), respectively. The phosphorylation of MEK1/2, the upstream kinase of ERK1/2, increased with exercise intensity (P<0.05) to 2.5+/-0.9 and 4.8+/-1.1 times the basal level at the low and high intensity, respectively. The statistical analysis revealed a systematic difference between basal, low and high intensity exercise levels for both kinases. There was no change in the phosphorylation of either kinase in the non-exercised leg. The phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB), a possible downstream target of the ERK/MAP kinase signalling pathway, was unaffected by exercise. The phosphorylation of ERK1/2 was significantly higher in purified freeze-dried compared to crude wet muscle after exercise, whereas the opposite pattern was observed for CREB. In conclusion, phosphorylation of ERK1/2 and MEK1/2 increases in an exercise intensity-dependent manner in human skeletal muscle and this seems to originate in the muscle fibres themselves.

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Section: Discussionsupporting

confidence: 54%

Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle

Widegren

Wretman

Lionikas

et al. 2000

Pfl�gers Archiv European Journal of Physiology

109

102

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“…cAMP levels were higher in senescent fibroblasts than young cells, and some forms of adenylyl cyclases also increased with age (Jang et al 2003). The abundance of the cAMP response element binding protein (CREB) is known to be markedly decreased in both whole cell and nuclear extracts of senescent fibroblasts (Chin et al 1996;Jang et al 2006). An adenylyl cyclase inhibitor was also induced senescent HDF proliferation by inhibiting adenosine monophosphate-activated protein kinase (AMPK) (Rhim et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Involvement of IGF binding protein 5 in prostaglandin E2-induced cellular senescence in human fibroblasts

et al. 2010

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Inflammation is an underlying basis for the molecular alterations that link aging and age-related pathological processes. In a previous study, we found that secretory phospholipase A(2) (sPLA(2)) induced cellular senescence in human dermal fibroblasts (HDFs). To further investigate the association of inflammation with cellular senescence, the effects of PGE(2) on cellular senescence in HDFs were investigated, since PGE(2) is the most abundant prostanoid. PGE(2) treatment induces cellular senescence, as determined by a decrease in cell proliferation and an increase in senescence-associated β-galactosidase staining. Notably, PGE(2) treatment increased the IGFBP5 protein level. While treatment with PGE(2) antagonists repressed PGE(2)-induced cellular senescence, increasing intracellular cAMP accelerated cellular senescence. Down-regulation of IGFBP5 inhibited PGE(2)-induced cellular senescence. Taken together, these results suggest that PGE(2) may play an important role in controlling cellular senescence of HDFs through the regulation of IGFBP5 and therefore may contribute to inflammatory disorders associated with aging.

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“…This is further validated by findings that decreased pCREB levels in the aged hippocampus can be significantly increased with lotus seedpod extract (Xu et al, 2010). Decreased CREB expression and CREB-mediated transcription has even been discovered in vitro using senescent IMR (Institute for Medical Research) fibroblasts, a cell line well characterized for its use in the molecular causes of aging (Chin et al, 1996b). CREB staining intensity has also been shown to be significantly decreased in the motor neurons of the spinal cord in the aged rat (Matsumoto, 2000).…”

Section: Altered Camp Levels Could Affect Pka and Creb Homeostasismentioning

confidence: 99%

Senescent-induced dysregulation of cAMP/CREB signaling and correlations with cognitive decline

Hansen

Zhang

2013

Brain Research

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It is well known that alongside senescence there is a gradual decline in cognitive ability, most noticeably certain kinds of memory such as working, episodic, spatial, and long term memory. However, until recently, not much has been known regarding the specific mechanisms responsible for the decline in cognitive ability with age. Over the past decades, researchers have become more interested in cAMP signaling, and its downstream transcription factor cAMP response element binding protein (CREB) in the context of senescence. However, there is still a lack of understanding on what ultimately causes the cognitive deficits observed with senescence. This review will focus on the changes in intracellular signaling in the brain, more specifically, alterations in cAMP/CREB signaling in aging. In addition, the downstream effects of altered cAMP signaling on cognitive ability with age will be further discussed. Overall, understanding the senescent-related changes that occur in cAMP/CREB signaling could be important for the development of novel drug targets for both healthy aging, and pathological aging such as Alzheimer's disease.

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Impaired cAMP-mediated gene expression and decreased cAMP response element binding protein in senescent cells

Cited by 44 publications

References 11 publications

Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle

Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle

Involvement of IGF binding protein 5 in prostaglandin E2-induced cellular senescence in human fibroblasts

Senescent-induced dysregulation of cAMP/CREB signaling and correlations with cognitive decline

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