CYP1A2 polymorphism and caffeine ingestion in relation to apoptosis markers after a resistance exercise in trained men: a randomized, double-blind, placebo-controlled, crossover study Caffeine, CYP1A2 polymorphism and exercise-induced apoptosis

Main Article Content

Mohammad Rahman Rahimi
Hassan Faraji
Tahseen Abdulkarim Amin AL-Zangana
Maryam Khodamoradi

Keywords

CYP1A2 polymorphism

Abstract

The objectives of this study was to determine the effects of caffeine ingestion and CYP1A2 polymorphism on Bax and Bcl-2 levels, as apoptosis markers, in acute resistance exercise (RE). In a randomized, double-blind, placebo-controlled, crossover study, fifteen trained men completed acute RE at 85% of 1RM. Subjects ingested either caffeine (CAF, 6 mg.kg−1 body mass) or placebo (PLA) one hour prior to exercise. Blood samples were taken pre-exercise (PRE), immediately post (POST), and 15 min (15 min POST) post RE for measurement of serum concentrations of Bax and Bcl-2 biomarkers. The CYP1A2 -163C>A polymorphisms were analyzed by amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) in genomic DNA samples which were isolated from the whole blood samples. Subjects were classified as either AA (n= 8) or AC/CC genotypes (n=7). At POST, Bax concentrations were significantly higher in PLA AA than PRE (p=0.014), CAF AA (p=0.003), CAF AC/CC (p=0.039) and PLA AA (p=0.034). No significant changes were observed in Bcl-2 levels at POST compared to PRE in both groups of CAF or PLA (p>0.05). However, Bcl-2 levels in 15 min POST were significantly higher in CAF AA than CAF AC/CC (p=0.003). Change percent of Bax/Bcl-2 ratio were significantly higher in PLA AC/CC at POST when compared with CAF AA (p=0.002) or CAF AC/CC (p=0.007), and were significantly lower in CAF AA at 15min POST than PLA AA (p=0.039). The findings indicate that exercise alone could accelerate apoptosis in the AC/CC group, whereas caffeine appears to attenuate susceptibility of cells to apoptosis.

Downloads

Download data is not yet available.
Abstract 296 | PDF Downloads 145

References

1. Phaneuf S, Leeuwenburgh C (2001) Apoptosis and exercise. Medicine and Science in Sports and Exercise 33 (3):393-396
2. Quadrilatero J, Alway SE, Dupont-Versteegden EE (2011) Skeletal muscle apoptotic response to physical activity: potential mechanisms for protection. Applied Physiology, Nutrition, and Metabolism 36 (5):608-617
3. Marín-García J, Goldenthal MJ (2008) Mitochondrial centrality in heart failure. Heart failure reviews 13 (2):137-150
4. Jafari A, Pourrazi H, Nikookheslat S, Baradaran B (2015) Effect of Exercise Training on Bcl-2 and Bax Gene Expression in the Rat Heart. Gene, Cell and Tissue 2 (4)
5. Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nature Reviews Molecular Cell Biology 9 (1):47-59
6. Rong Y, Distelhorst CW (2008) Bcl-2 protein family members: versatile regulators of calcium signaling in cell survival and apoptosis. Annual Review of Physiology 70:73-91
7. Bagci E, Vodovotz Y, Billiar T, Ermentrout G, Bahar I (2006) Bistability in apoptosis: roles of bax, bcl-2, and mitochondrial permeability transition pores. Biophysical Journal 90 (5):1546-1559
8. Stefanello S, Soares F, Barcelos R (2016) Caffeine supplementation changes inflammatory biomarkers after exercise. J Yoga Phys Ther 6 (240):2
9. Sestili P, Martinelli C, Colombo E, Barbieri E, Potenza L, Sartini S, Fimognari C (2011) Creatine as an antioxidant. Amino acids 40 (5):1385-1396
10. Guimaraes-Ferreira L, Pinheiro CHJ, Gerlinger-Romero F, Vitzel KF, Nachbar RT, Curi R, Nunes MT (2012) Short-term creatine supplementation decreases reactive oxygen species content with no changes in expression and activity of antioxidant enzymes in skeletal muscle. European Journal of Applied Physiology 112 (11):3905-3911
11. Sheikholeslami-Vatani D, Faraji H (2018) Influence of Creatine Supplementation on Apoptosis Markers after Downhill Running in Middle-Aged Men: A Crossover Randomized, Double-Blind, and Placebo-Controlled Study. American journal of physical medicine & rehabilitation
12. Rahimi R, Mirzaei B, Rahmani-Nia F, Salehi Z (2015) Effects of creatine monohydrate supplementation on exercise-induced apoptosis in athletes: A randomized, double-blind, and placebo-controlled study. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences 20 (8):733
13. Jiang J, Lan Y, Zhang T, Yu M, Liu X, Li L, Chen X (2015) The in vitro effects of caffeine on viability, cycle cycle profiles, proliferation, and apoptosis of glioblastomas. Eur Rev Med Pharmacol Sci 19 (17):3201-3207
14. Corsetti G, Pasini E, Assanelli D, Bianchi R (2008) Effects of acute caffeine administration on NOS and Bax/Bcl2 expression in the myocardium of rat. Pharmacological research 57 (1):19-25
15. Rahimi R (2018) The effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance exercise: a randomized, double-blind, placebo-controlled, crossover study. Irish Journal of Medical Science (1971-):1-9
16. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (2006) Coffee, CYP1A2 genotype, and risk of myocardial infarction. Jama 295 (10):1135-1141
17. Guest N, Corey P, Vescovi J, El-Sohemy A (2018) Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes. Medicine and science in sports and exercise
18. Sachse C, Brockmöller J, Bauer S, Roots I (1999) Functional significance of a C→ A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. British journal of clinical pharmacology 47 (4):445-449
19. Womack CJ, Saunders MJ, Bechtel MK, Bolton DJ, Martin M, Luden ND, Dunham W, Hancock M (2012) The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine. Journal of the International Society of Sports Nutrition 9 (1):7
20. Graham TE (2001) Caffeine and exercise. Sports medicine 31 (11):785-807
21. Teekachunhatean S, Tosri N, Rojanasthien N, Srichairatanakool S, Sangdee C (2013) Pharmacokinetics of caffeine following a single administration of coffee enema versus oral coffee consumption in healthy male subjects. ISRN pharmacology 2013
22. Mora-Rodríguez R, Pallarés JG, López-Samanes Á, Ortega JF, Fernández-Elías VE (2012) Caffeine ingestion reverses the circadian rhythm effects on neuromuscular performance in highly resistance-trained men. PLoS One 7 (4):e33807
23. Medrano RFV, de Oliveira CA (2014) Guidelines for the tetra-primer ARMS–PCR technique development. Molecular biotechnology 56 (7):599-608
24. Sharafi H, Rahimi R (2012) The effect of resistance exercise on p53, caspase-9, and caspase-3 in trained and untrained men. The Journal of Strength & Conditioning Research 26 (4):1142-1148
25. Boroujerdi S, Rahimi R (2011) The apoptotic response to resistance exercise with different intensities in athletes. Medcina dello Sport 64 (1):31-44
26. Sari-Sarraf V, Amirsasan R, Sheikholeslami-Vatani D, Faraji H (2016) Effect of creatine supplementation on the factors involved in apoptosis-related process (Bax, Bcl-2) and their ratio (Bcl-2/Bax) during acute resistance exercise in middle-aged men. Scientific Journal of Kurdistan University of Medical Sciences 21 (4)
27. Podhorska-Okolow M, Dzlegiel P, Gomulkiewicz A, Kisiela D, Dolinska-Krajewska B, Jethon Z, Carraro U, Zabel M (2006) Exercise-induced apoptosis in rat kidney is mediated by both angiotensin II AT1 and AT2 receptors. Histology and histopathology 21 (4/6):459
28. Sheikholeslami-Vatani D, Ahmadi S, Faraji H (2018) The Effects of Omega-3 and Branched-Chain Amino Acids Supplementation on Serum Apoptosis Markers Following Acute Resistance Exercise in Old Men. Journal of aging and physical activity:1-23
29. Faraji H, Rahimi R, Sheikholeslami-Vatani D, Jafaari A (2016) Apoptosis response to different rest periods after resistance exercise in athletes. - 69 (2):173-183
30. Kerksick C, Taylor L, Harvey A, Willoughby D (2008) Gender-related differences in muscle injury, oxidative stress, and apoptosis. Medicine and Science in Sports and Exercise 40 (10):1772
31. Kerksick C, Kreider RB, Willoughby DS (2010) Intramuscular adaptations to eccentric exercise and antioxidant supplementation. Amino Acids 39 (1):219-232
32. Park K-S, Sedlock DA, Navalta JW, Lee M-G, Kim S-H (2011) Leukocyte apoptosis and pro-/anti-apoptotic proteins following downhill running. European journal of applied physiology 111 (9):2349-2357
33. Gogvadze V, Orrenius S, Zhivotovsky B (2006) Multiple pathways of cytochrome c release from mitochondria in apoptosis. Biochimica Et Biophysica Acta (BBA)-Bioenergetics 1757 (5):639-647
34. Zhou S-F, Wang B, Yang L-P, Liu J-P (2010) Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug metabolism reviews 42 (2):268-354
35. Cornelis MC, Bae S-C, Kim I, El-Sohemy A (2010) CYP1A2 genotype and rheumatoid arthritis in Koreans. Rheumatology international 30 (10):1349-1354
36. Jafari M, Rabbani A (2004) Studies on the mechanism of caffeine action in alveolar macrophages: caffeine elevates cyclic adenosine monophosphate level and prostaglandin synthesis. Metabolism 53 (6):687-692
37. Tichý A, Muthná D, Vávrová J, Pejchal J, Šinkorová Z, Zárybnická L, Řezáčová M (2011) Caffeine-suppressed ATM pathway leads to decreased p53 phosphorylation and increased programmed cell death in gamma-irradiated leukaemic molt-4 cells. Journal of Applied Biomedicine 9 (1):49-56
38. Barcelos RP, Souza MA, Amaral GP, Stefanello ST, Bresciani G, Fighera MR, Soares FAA, Barbosa NV (2014) Caffeine supplementation modulates oxidative stress markers in the liver of trained rats. Life sciences 96 (1):40-45
39. Yenisetti S (2016) Beneficial Role of Coffee and Caffeine in Neurodegenerative Diseases: A Minireview.
40. Dubrez L, Coll J-L, Hurbin A, Solary E, Favrot M-C (2001) Caffeine sensitizes human H358 cell line to p53-mediated apoptosis by inducing mitochondrial translocation and conformational change of BAX protein. Journal of Biological Chemistry 276 (42):38980-38987
41. Khodapasand E, Jafarzadeh N, Farrokhi F, Kamalidehghan B, Houshmand M (2015) Is Bax/Bcl-2 ratio considered as a prognostic marker with age and tumor location in colorectal cancer? Iranian biomedical journal 19 (2):69
42. Portier BP, Taglialatela G (2006) Bcl-2 localized at the nuclear compartment induces apoptosis after transient overexpression. Journal of Biological Chemistry 281 (52):40493-40502
43. Irmawati A, Nadira Jasmin S (2018) The effect of moderate exercise on the elevation of Bax/Bcl-2 ratio in oral squamous epithelial cells induced by benzopyrene. Veterinary world 11 (2):177
44. Corsetti G, Pasini E, Assanelli D, Saligari E, Adobati M, Bianchi R (2007) Acute caffeine administration decreased NOS and Bcl2 expression in rat skeletal muscles. Pharmacological research 55 (2):96-103
45. Koda M, Iwasaki M, Yamano Y, Lu X, Katoh T (2017) Association between NAT2, CYP1A1, and CYP1A2 genotypes, heterocyclic aromatic amines, and prostate cancer risk: a case control study in Japan. Environmental health and preventive medicine 22 (1):72
46. Czabotar PE, Lessene G, Strasser A, Adams JM (2014) Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nature reviews Molecular cell biology 15 (1):49-63
47. Fernandez M, Lopez A, Santa‐Maria A (2003) Apoptosis induced by different doses of caffeine on Chinese hamster ovary cells. Journal of Applied Toxicology 23 (4):221-224