Update on caffeine consumption, disposition and action

Mandel, H. George

doi:10.1016/s0278-6915(02)00093-5

Cited by 203 publications

(129 citation statements)

References 10 publications

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“…Bartkova and coworkers recently demonstrated that caffeine in the drinking water can inhibit ATM activation and stimulate the development of larger and more invasive tumors using a Ras-driven xenograft mouse model. Interestingly, the dose of caffeine (approximately 15 mg/kg/day) used in that experiment is physiologically relevant and similar to the amount consumed by a heavy coffee drinker (Mandel, 2002). Similar to those findings, we found that the same concentration of caffeine also promoted de novo tumorigenesis in K5 E2F3a transgenic mice.…”

Section: Discussionsupporting

confidence: 88%

Transgenic expression of E2F3a causes DNA damage leading to ATM-dependent apoptosis

et al. 2008

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Many early stage human tumors display markers of a DNA-damage response (DDR), including ataxia telangiectasia mutated (ATM) kinase activation. This suggests that DNA damage accumulates during the process of carcinogenesis and that the ATM-dependent response to this damage may function to suppress cancer progression. The E2F3a transcription factor plays an important role in regulating cell proliferation and is amplified in a subset of human cancers. Similar to human premalignant lesions, we find activated ATM and other markers of the DDR in the hyperplastic epidermis of transgenic mice expressing E2F3a through a keratin 5 (K5) promoter. Primary keratinocytes from K5 E2F3a transgenic mice contain increased levels of DNA breaks compared to wild-type cells. E2F3a overexpression also induced DNA damage in primary human fibroblasts that was inhibited by blocking DNA replication. The absence of ATM impaired apoptosis induced by E2F3a and treating K5 E2F3a transgenic mice with caffeine, an inhibitor of ATM and Rad3-related (ATR), promoted skin tumor development. These findings demonstrate that the deregulated expression of E2F3a causes DNA damage under physiological conditions and indicate that the ATM-dependent response to this damage is important for the induction of apoptosis and tumor suppression.

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Section: Discussionsupporting

confidence: 88%

Transgenic expression of E2F3a causes DNA damage leading to ATM-dependent apoptosis

et al. 2008

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“…The estimated overall caffeine intake is 200-250 mg/person per day in the USA and Canada, and 300-400 mg/person per day in Northern Europe and Great Britain (26,27). The caffeine concentration applied for in vivo experiments (10 mg/kg) and the dose used for in vitro experiments (10 -4 M) correspond to intake of 250 mg caffeine or 2-3 cups of coffee by a human weighing 70 kg (15, 18-20, 25, 26); hence the caffeine concentrations applied in the presented experiments are physiologically relevant.…”

Section: Discussionmentioning

confidence: 99%

Caffeine induces endothelial tissue factor expression via phosphatidylinositol 3-kinase inhibition

Gebhard¹,

Holy²,

Camici³

et al. 2012

Thromb Haemost

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SummaryTissue factor (TF) is the key activator of coagulation and is involved in acute coronary syndromes. Caffeine is often reported to increase cardiovascular risk; however, its effect on cardiovascular morbidity and mortality is controversial. Hence, this study was designed to investigate the impact of caffeine on endothelial TF expression in vitro. Caffeine concentration-dependently enhanced TF protein expression and surface activity in human endothelial cells stimulated by tumour necrosis factor (TNF)-α or thrombin. Caffeine inhibited phosphatidylinositol 3-kinase (PI3K) activity and this effect was comparable to that of the known PI3K inhibitor LY294002. Consistently, treatment of endothelial cells with LY294002 enhanced TNF-α induced TF expression to a similar extent as caffeine, and adenoviral expression of the active PI3K mutant (p110) reversed the effect of both caffeine and LY294002 on TF expression. Caffeine and LY294002 increased DNA binding capacity of the transcription factor nuclear factor κB, whereas the activation pattern of mitogen-activated protein kinases (MAPK) remained unaltered. Luciferase reporter assay revealed a caffeine dependent activation of the TF promoter, and RT-PCR revealed a dose dependent increase in TF mRNA levels when stimulated with caffeine in the presence of TNF-α. In conclusion, caffeine enhances TNF-α-induced endothelial TF protein expression as well as surface activity by inhibition of PI3K signalling. Since the caffeine concentrations applied in the present study are within the plasma range measured in humans, our findings indicate that caffeine enhances the prothrombotic potential of endothelial cells and underscore the importance of PI3K in mediating these effects.

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“…Caffeine, present in several food items ingested daily 1 can be used to increase physical performance 2 , and effect that could be related to the antagonism of adenosine receptors in the central nervous system, increasing the release of dopaminergic neurotransmitters an affecting the perception of effort. 4 Furthermore, caffeine acts on the propagation of neural signals between the brain and the neuromuscular junction 5 and on the musculoskeletal system, facilitating stimulation and contraction.…”

Section: Introductionmentioning

confidence: 99%

Caffeine and physical training: effects on cardiac morphology and cardiovascular response

Ruíz¹,

Ramos

Martins‐Pinge

et al. 2014

Rev. Assoc. Med. Bras.

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Conflict of interest: noneObjective: to analyze the morphological structure of cardiac, blood pressure (BP), heart rate (HR) and heart rate variability (HRV) of rats subjected to physical training with supplementation of caffeine. Methods: 60 rats were divided into 4 groups: control (CO), control with caffeine (CAF), trained control (TRE) and trained with caffeine (TCAF). All trained groups underwent 4 weeks of swimming, and all caffeine groups were supplemented by voluntary ingestion of caffeine diluted in drinking water. Results: there were no changes to BP and HR between groups. Regarding HRV, there was a decrease in LFnorm (low frequency) and LF/HF ratio (low and high frequency) in TCAF and CAF compared to group (p<0.02 and p<0.03, respectively). An increase occurred in CAF compared to the CO in the component LFnorm (p<0.05). The results also showed an increase in the relative weight of heart in the TRE (p<0.04) and TCAF (p<0.03) compared to CO. Conclusion: caffeine did not modify the hemodynamic responses. However, physical training resulted in a decrease in sympathetic response and an increase in relative heart weight.Uniterms: caffeine; exercise; arterial blood pressure; heart rate.

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Update on caffeine consumption, disposition and action

Cited by 203 publications

References 10 publications

Transgenic expression of E2F3a causes DNA damage leading to ATM-dependent apoptosis

Transgenic expression of E2F3a causes DNA damage leading to ATM-dependent apoptosis

Caffeine induces endothelial tissue factor expression via phosphatidylinositol 3-kinase inhibition

Caffeine and physical training: effects on cardiac morphology and cardiovascular response

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