Journal of Veterinary Science

  • 제23권6호
  • /
  • Pages.84.1-84.15
  • /
  • 2022
  • /
  • 1229-845X(pISSN)
  • /
  • 1976-555X(eISSN)
대한수의학회 (The Korean Society of Veterinary Science)
권호 표지
DOI QR코드

DOI QR Code

Chlorogenic acid alleviates the reduction of Akt and Bad phosphorylation and of phospho-Bad and 14-3-3 binding in an animal model of stroke

  • Murad-Ali, Shah (Department of Anatomy and Histology, College of Veterinary Medicine, Gyeongsang National University) ;
  • Ju-Bin, Kang (Department of Anatomy and Histology, College of Veterinary Medicine, Gyeongsang National University) ;
  • Myeong-Ok, Kim (Division of Life Science and Applied Life Science, College of Natural Sciences, Gyeongsang National University) ;
  • Phil-Ok, Koh (Department of Anatomy and Histology, College of Veterinary Medicine, Gyeongsang National University)
  • 투고 : 2022.07.27
  • 심사 : 2022.09.15
  • 발행 : 2022.11.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: Stroke is caused by disruption of blood supply and results in permanent disabilities as well as death. Chlorogenic acid is a phenolic compound found in various fruits and coffee and exerts antioxidant, anti-inflammatory, and anti-apoptotic effects. Objectives: The purpose of this study was to investigate whether chlorogenic acid regulates the PI3K-Akt-Bad signaling pathway in middle cerebral artery occlusion (MCAO)-induced damage. Methods: Chlorogenic acid (30 mg/kg) or vehicle was administered peritoneally to adult male rats 2 h after MCAO surgery, and animals were sacrificed 24 h after MCAO surgery. Neurobehavioral tests were performed, and brain tissues were isolated. The cerebral cortex was collected for Western blot and immunoprecipitation analyses. Results: MCAO damage caused severe neurobehavioral disorders and chlorogenic acid improved the neurological disorders. Chlorogenic acid alleviated the MCAO-induced histopathological changes and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Furthermore, MCAO-induced damage reduced the expression of phospho-PDK1, phospho-Akt, and phospho-Bad, which was alleviated with administration of chlorogenic acid. The interaction between phospho-Bad and 14-3-3 levels was reduced in MCAO animals, which was attenuated by chlorogenic acid treatment. In addition, chlorogenic acid alleviated the increase of cytochrome c and caspase-3 expression caused by MCAO damage. Conclusions: The results of the present study showed that chlorogenic acid activates phospho-Akt and phospho-Bad and promotes the interaction between phospho-Bad and 14-3-3 during MCAO damage. In conclusion, chlorogenic acid exerts neuroprotective effects by activating the Akt-Bad signaling pathway and maintaining the interaction between phospho-Bad and 14-3-3 in ischemic stroke model.

키워드

과제정보

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST; NRF-2021R1F1A105878711).

참고문헌

  1. Ingall T. Stroke--incidence, mortality, morbidity and risk. J Insur Med. 2004;36(2):143-152.
  2. Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin. 2008;26(4):871-895. https://doi.org/10.1016/j.ncl.2008.07.003
  3. Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci. 2017;38(7):1167-1186. https://doi.org/10.1007/s10072-017-2938-1
  4. Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia. Stroke. 2009;40(5):e331-e339.
  5. Chan PH. Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Neurochem Res. 2004;29(11):1943-1949.
  6. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoformspecific PI3K signalling. Nat Rev Mol Cell Biol. 2010;11(5):329-341. https://doi.org/10.1038/nrm2882
  7. Wick MJ, Dong LQ, Riojas RA, Ramos FJ, Liu F. Mechanism of phosphorylation of protein kinase B/Akt by a constitutively active 3-phosphoinositide-dependent protein kinase-1. J Biol Chem. 2000;275(51):40400-40406.
  8. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev. 1999;13(22):2905-2927. https://doi.org/10.1101/gad.13.22.2905
  9. Franke TF, Kaplan DR, Cantley LC. PI3K: downstream AKTion blocks apoptosis. Cell. 1997;88(4):435-437. https://doi.org/10.1016/S0092-8674(00)81883-8
  10. Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell. 1995;80(2):285-291. https://doi.org/10.1016/0092-8674(95)90411-5
  11. Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell. 1996;87(4):619-628. https://doi.org/10.1016/S0092-8674(00)81382-3
  12. Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB, et al. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell. 2000;6(1):41-51. https://doi.org/10.1016/S1097-2765(05)00012-2
  13. Kamada H, Nito C, Endo H, Chan PH. Bad as a converging signaling molecule between survival PI3-K/Akt and death JNK in neurons after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 2007;27(3):521-533. https://doi.org/10.1038/sj.jcbfm.9600367
  14. Clifford MN. Chlorogenic acids and other cinnamates-nature, occurrence and dietary burden. J Sci Food Agric. 1999;79(3):362-372. https://doi.org/10.1002/(SICI)1097-0010(19990301)79:3<362::AID-JSFA256>3.0.CO;2-D
  15. Liang N, Kitts DD. Role of chlorogenic acids in controlling oxidative and inflammatory stress conditions. Nutrients. 2015;8(1):16.
  16. Miao M, Cao L, Li R, Fang X, Miao Y. Protective effect of chlorogenic acid on the focal cerebral ischemia reperfusion rat models. Saudi Pharm J. 2017;25(4):556-563. https://doi.org/10.1016/j.jsps.2017.04.023
  17. Shah MA, Kang JB, Park DJ, Kim MO, Koh PO. Chlorogenic acid alleviates cerebral ischemia-induced neuroinflammation via attenuating nuclear factor kappa B activation. Neurosci Lett. 2022;773:136495.
  18. Shah MA, Kang JB, Park DJ, Kim MO, Koh PO. Chlorogenic acid alleviates neurobehavioral disorders and brain damage in focal ischemia animal models. Neurosci Lett. 2021;760:136085.
  19. Han D, Chen W, Gu X, Shan R, Zou J, Liu G, et al. Cytoprotective effect of chlorogenic acid against hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells through PI3K/Akt-mediated Nrf2/HO-1 signaling pathway. Oncotarget. 2017;8(9):14680-14692. https://doi.org/10.18632/oncotarget.14747
  20. Lee K, Lee JS, Jang HJ, Kim SM, Chang MS, Park SH, et al. Chlorogenic acid ameliorates brain damage and edema by inhibiting matrix metalloproteinase-2 and 9 in a rat model of focal cerebral ischemia. Eur J Pharmacol. 2012;689(1-3):89-95. https://doi.org/10.1016/j.ejphar.2012.05.028
  21. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84-91. https://doi.org/10.1161/01.STR.20.1.84
  22. Shamsaei N, Erfani S, Fereidoni M, Shahbazi A. Neuroprotective effects of exercise on brain edema and neurological movement disorders following the cerebral ischemia and reperfusion in rats. Basic Clin Neurosci. 2017;8(1):77-84.
  23. Michalski D, Kuppers-Tiedt L, Weise C, Laignel F, Hartig W, Raviolo M, et al. Long-term functional and neurological outcome after simultaneous treatment with tissue-plasminogen activator and hyperbaric oxygen in early phase of embolic stroke in rats. Brain Res. 2009;1303:161-168. https://doi.org/10.1016/j.brainres.2009.09.038
  24. Zhang L, Chen J, Li Y, Zhang ZG, Chopp M. Quantitative measurement of motor and somatosensory impairments after mild (30 min) and severe (2 h) transient middle cerebral artery occlusion in rats. J Neurol Sci. 2000;174(2):141-146. https://doi.org/10.1016/S0022-510X(00)00268-9
  25. Takeshita H, Yamamoto K, Nozato S, Inagaki T, Tsuchimochi H, Shirai M, et al. Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice. Sci Rep. 2017;7(1):42323.
  26. Park DJ, Kang JB, Shah FA, Koh PO. Resveratrol modulates the Akt/GSK-3β signaling pathway in a middle cerebral artery occlusion animal model. Lab Anim Res. 2019;35(1):18. https://doi.org/10.1186/s42826-019-0017-x
  27. Koh PO. Melatonin prevents hepatic injury-induced decrease in Akt downstream targets phosphorylations. J Pineal Res. 2011;51(2):214-219. https://doi.org/10.1111/j.1600-079X.2011.00879.x
  28. Koh PO. Ferulic acid prevents the cerebral ischemic injury-induced decrease of Akt and Bad phosphorylation. Neurosci Lett. 2012;507(2):156-160. https://doi.org/10.1016/j.neulet.2011.12.012
  29. Lee TK, Kang IJ, Kim B, Sim HJ, Kim DW, Ahn JH, et al. Experimental pretreatment with chlorogenic acid prevents transient ischemia-induced cognitive decline and neuronal damage in the hippocampus through anti-oxidative and anti-inflammatory effects. Molecules. 2020;25(16):3578.
  30. Gao J, He X, Ma Y, Zhao X, Hou X, Hao E, et al. Chlorogenic acid targeting of the AKT PH domain activates AKT/GSK3β/FOXO1 signaling and improves glucose metabolism. Nutrients. 2018;10(10):1366.
  31. Samuel T, Weber HO, Rauch P, Verdoodt B, Eppel JT, McShea A, et al. The G2/M regulator 14-3-3sigma prevents apoptosis through sequestration of Bax. J Biol Chem. 2001;276(48):45201-45206. https://doi.org/10.1074/jbc.M106427200
  32. Downward J. How BAD phosphorylation is good for survival. Nat Cell Biol. 1999;1(2):E33-E35. https://doi.org/10.1038/10026
  33. Fan J, Xu G, Nagel DJ, Hua Z, Zhang N, Yin G. A model of ischemia and reperfusion increases JNK activity, inhibits the association of BAD and 14-3-3, and induces apoptosis of rabbit spinal neurocytes. Neurosci Lett. 2010;473(3):196-201.