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Salimi, Rahil, Shirpoor, Alireza, Naderi, Roya. (1404). miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid. سامانه مدیریت نشریات علمی, 80(4), 945-955. doi: 10.32592/ARI.2025.80.4.945
Rahil Salimi; Alireza Shirpoor; Roya Naderi. "miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid". سامانه مدیریت نشریات علمی, 80, 4, 1404, 945-955. doi: 10.32592/ARI.2025.80.4.945
Salimi, Rahil, Shirpoor, Alireza, Naderi, Roya. (1404). 'miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid', سامانه مدیریت نشریات علمی, 80(4), pp. 945-955. doi: 10.32592/ARI.2025.80.4.945
Salimi, Rahil, Shirpoor, Alireza, Naderi, Roya. miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid. سامانه مدیریت نشریات علمی, 1404; 80(4): 945-955. doi: 10.32592/ARI.2025.80.4.945

miR‑429 and GATA4 may participate in cerebral ischemic stroke by regulating autophagy and apoptosis: the effect of Chlorogenic acid

Archives of Razi Institute
مقاله 16، دوره 80، شماره 4، مهر و آبان 2025، صفحه 945-955    اصل مقاله (645.11 K)
نوع مقاله: Original Articles
شناسه دیجیتال (DOI): 10.32592/ARI.2025.80.4.945
نویسندگان
Rahil Salimi1؛ Alireza Shirpoor2؛ Roya Naderi* 2، 3
1Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.
2Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
3Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
چکیده
Abstract
Autophagy is a double-edged sword for maintaining neural system homeostasis during development of cerebral ischemia. However, the potential molecular mechanisms behind that remain unclear. This study investigated the miR-429 and its target GATA4 alterations, autophagy mediators and apoptosis in ischemic stroke alone and also in combination with chlorogenic acid (CGA).
Male Wistar rats were assigned into three groups (n=8): sham, IR (ischemia-reperfusion, ischemia-reperfusion, transient cerebral ischemia inducing by common carotid artery occlusion and reperfusion), IR+CGA (30 mg/kg, ip; intraperitoneally, 10 minutes prior to ischemia and 10 minutes before reperfusion.). miR-429, GATA4, c-Caspase-3/p-Caspase-3 ratio, LC3-I, LC3-II, Beclin1 and p62 measured by Real time PCR and also Western blot assays. At the end of the experiment, we observed increased miR-429 gene expression (P<0.05) and c-Caspase-3/p-Caspase-3 ratio (P<0.01) as well as decreased GATA4 protein expression (P<0.001) in IR group. In addition, autophagy was over-activated markedly in the brain of CCAO rats as evidenced by an increased ratio of LC3-II/I and Beclin1 protein expression and decreased expression of p62 after 24 h of reperfusion (P<0.001). Moreover, immunohistochemistry studies found that cerebral IR significantly increased the ratio of total LC3 immunoreactivity in the cortex tissue of male rats (P<0.001). Treatment with CGA significantly attenuated autophagic activity as well as apoptosis and reversed aforementioned molecule levels. Taken together, these results suggested that ischemic insult can increase autophagic activities and apoptosis possibly by miR‑429 and GATA4 alterations in the brain cortex after cerebral IR insult which can be alleviated by CGA as a potential therapy for someone afflicted with ischemia.
کلیدواژه‌ها
ischemia-reperfusion؛ brain؛ chlorogenic acid
عنوان مقاله [English]
نقش miR‑429 و GATA4 در سکته مغزی ایسکمیک از طریق اتوفاژی و آپوپتوز: اثر اسید کلروژنیک
چکیده [English]
اتوفاژی یک شمشیر دولبه برای حفظ هموستاز سیستم عصبی در طول ایجاد ایسکمی مغزی است. با این حال، مکانیسم‌های مولکولی بالقوه پشت آن نامشخص است. این مطالعه به بررسی miR-429 و تغییرات GATA4 و همچنین واسطه‌های اتوفاژی و آپوپتوز در سکته مغزی ایسکمیک به تنهایی و در ترکیب با اسید کلروژنیک (CGA) پرداخت. موش های صحرایی نر نژاد ویستار به سه گروه تقسیم شدند (در هر گروه 8 موش): گروه شم، ایسکمی-ریپرفیوژن ( با بستن هر دو شریان کاروتید مشترک)، ایسکمی-ریپرفیوژن+CGA (با دوز 30 میلی گرم بر کیلوگرم بصورت داخل صفاقی ده دقیقه قبل از ایسکمی و ده دقیقه قبل از خونرسانی مجدد). miR-429، GATA4، c-Caspase-3/p-Caspase-3، LC3-I، LC3-II، Beclin1 و p62 توسط Real Time PCR و Western blot اندازه گیری شد. افزایش بیان ژن (P<0.05)miR-429 و c-Caspase-3/p-Caspase-3 (P<0.01) و همچنین کاهش بیان پروتئین GATA4 (P<0.001) در گروه IR مشاهده شد. علاوه بر این، اتوفاژی در مغز CCAO افزایش داشت که با افزایش نسبت LC3-II/I و بیان پروتئین Beclin1 و کاهش بیان p62 پس از 24 ساعت خون‌رسانی مجدد نشان داد (P<0.001) . علاوه بر این، مطالعات ایمونوهیستوشیمی نشان داد که IR مغزی به طور قابل‌توجهی مقدار کل LC3 را در بافت قشر موش‌های نر افزایش داد (P<0.001) . درمان با CGA به طور قابل توجهی فعالیت اتوفاژیک و همچنین آپوپتوز را کاهش داد و سطوح مولکولی فوق را معکوس کرد. در مجموع، این نتایج نشان داد که ایسکمی می‌تواند فعالیت‌های اتوفاژیک و آپوپتوز را احتمالاً با تغییرات miR-429 و GATA4 در قشر مغز پس از آسیب IR مغزی افزایش دهد که توسط CGA به عنوان یک درمان بالقوه برای افرادی که به ایسکمی مبتلا هستند کاهش یابد.
کلیدواژه‌ها [English]
ایسکمی-ریپرفیوژن, مغز, اسید کلروژنیک
سایر فایل های مرتبط با مقاله
مراجع
  1. Salimi R, Naderi R, Shirpoor A. Involvement of miR-27a/smurf1/ TNF-α and mitochondrial apoptotic pathway in apoptosis induced by cerebral ischemia-reperfusion injury in rats: The protective effect of chlorogenic acid. Neuroscience letters. 2023;817:137529.https://doi.org/10.1016/j.neulet.2023.137529.
  2. Rad AK, Mehrjerdi HK, Pedram MS, Azizzadeh M, Amanollahi S. Clinical Evaluation of the Effect of Methylprednisolone Sodium Succinate and Meloxicam in Experimental Acute Spinal Cord Injury. Iranian Journal of Veterinary Medicine. 2023;17(2)
  3. Schmitz KJ, Ademi C, Bertram S, Schmid KW, Baba HA. Prognostic relevance of autophagy-related markers LC3, p62/sequestosome 1, Beclin-1 and ULK1 in colorectal cancer patients with respect to KRAS mutational status. World journal of surgical oncology. 2016;14(1):189.https://doi.org/10.1186/s12957-016-0946-x.
  4. Zhao G, Zhang W, Li L, Wu S, Du G. Pinocembrin protects the brain against ischemia-reperfusion injury and reverses the autophagy dysfunction in the penumbra area. Molecules (Basel, Switzerland). 2014;19(10):15786-98.https://doi.org/10.3390/molecules191015786.
  5. Qi R, Wang X. Inhibition of miR-429 improves neurological recovery of traumatic brain injury mice and attenuates microglial neuroinflammation. International immunopharmacology. 2020;79:106091.https://doi.org/10.1016/j.intimp.2019.106091.
  6. Sun H, Zhong D, Wang C, Sun Y, Zhao J, Li G. MiR-298 Exacerbates Ischemia/Reperfusion Injury Following Ischemic Stroke by Targeting Act1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2018;48(2):528-39.https://doi.org/10.1159/000491810.
  7. Xiao J, Kong R, Hu J. Inhibition of microRNA-429 attenuates oxygen-glucose deprivation/reoxygenation-induced neuronal injury by promoting expression of GATA-binding protein 4. Neuroreport. 2018;29(9):723-30.https://doi.org/10.1097/wnr.0000000000001023.
  8. Zhu Q, Hu F. Antagonism of miR-429 ameliorates anoxia/reoxygenation injury in cardiomyocytes by enhancing MO25/LKB1/AMPK mediated autophagy. Life sciences. 2019;235:116842.https://doi.org/10.1016/j.lfs.2019.116842.
  9. Agnihotri S, Wolf A, Picard D, Hawkins C, Guha A. GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system. Oncogene. 2009;28(34):3033-46.https://doi.org/10.1038/onc.2009.159.
  10. Kobayashi S, Lackey T, Huang Y, Bisping E, Pu WT, Boxer LM, et al. Transcription factor gata4 regulates cardiac BCL2 gene expression in vitro and in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006;20(6):800-2.https://doi.org/10.1096/fj.05-5426fje.
  11. Kobayashi S, Volden P, Timm D, Mao K, Xu X, Liang Q. Transcription factor GATA4 inhibits doxorubicin-induced autophagy and cardiomyocyte death. The Journal of biological chemistry. 2010;285(1):793-804.https://doi.org/10.1074/jbc.M109.070037.
  12. Kumar G, Mukherjee S, Paliwal P, Singh SS, Birla H, Singh SP, et al. Neuroprotective effect of chlorogenic acid in global cerebral ischemia-reperfusion rat model. 2019;392(10):1293-309.https://doi.org/10.1007/s00210-019-01670-x.
  13. Mojibi R, Mehrzad J, Sharifzadeh A, Nikaein D. Apoptotic Effects of Caffeic Acid Phenethyl Ester and Matricaria chamomilla Essential Oil on A549 Non-Small Cell Lung Cancer Cells. Iranian Journal of Veterinary Medicine. 2022;16(4)
  14. Song J, Zhou N, Ma W, Gu X, Chen B, Zeng Y, et al. Modulation of gut microbiota by chlorogenic acid pretreatment on rats with adrenocorticotropic hormone induced depression-like behavior. Food & function. 2019;10(5):2947-57.https://doi.org/10.1039/c8fo02599a.
  15. Rebai O, Amri M. Chlorogenic Acid Prevents AMPA-Mediated Excitotoxicity in Optic Nerve Oligodendrocytes Through a PKC and Caspase-Dependent Pathways. Neurotoxicity research. 2018;34(3):559-73.https://doi.org/10.1007/s12640-018-9911-5.
  16. 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. European journal of pharmacology. 2012;689(1-3):89-95.https://doi.org/10.1016/j.ejphar.2012.05.028.
  17. Hermawati E, Arfian N, Mustofa M, Partadiredja G. Chlorogenic acid ameliorates memory loss and hippocampal cell death after transient global ischemia. The European journal of neuroscience. 2020;51(2):651-69.https://doi.org/10.1111/ejn.14556.
  18. Cui DR, Wang L, Jiang W, Qi AH, Zhou QH, Zhang XL. Propofol prevents cerebral ischemia-triggered autophagy activation and cell death in the rat hippocampus through the NF-κB/p53 signaling pathway. Neuroscience. 2013;246:117-32.https://doi.org/10.1016/j.neuroscience.2013.04.054
  19. Alabdaly Y, AL-hbiti T, Kaleel HI. Fluconazole Toxicity in Rat Model: Histopathological and Neurobehavioral Effects. Iranian Journal of Veterinary Medicine. 2023
  20. Ghotbitabar Z, Asghari A, Hassanpour S, Jahandideh A. Effects of Quebracho Tannin Extract on Testicular Ischemia-/Reperfusion. Iranian Journal of Veterinary Medicine. 2022;16(4)
  21. He CL, Tang Y, Wu JM, Long T, Yu L, Teng JF, et al. Chlorogenic acid delays the progression of Parkinson's disease via autophagy induction in Caenorhabditis elegans. Nutritional neuroscience. 2021;10.1080/1028415x.2021.2009993:1-14.https://doi.org/10.1080/1028415x.2021.2009993.
  22. Tao J, Shen C, Sun Y, Chen W, Yan G. Neuroprotective effects of pinocembrin on ischemia/reperfusion-induced brain injury by inhibiting autophagy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018;106:1003-10.https://doi.org/10.1016/j.biopha.2018.07.026.
  23. Ji X, Wang B, Paudel YN, Li Z, Zhang S, Mou L, et al. Protective Effect of Chlorogenic Acid and Its Analogues on Lead-Induced Developmental Neurotoxicity Through Modulating Oxidative Stress and Autophagy. Frontiers in molecular biosciences. 2021;8:655549.https://doi.org/10.3389/fmolb.2021.655549.
  24. Gao L, Li X, Meng S, Ma T, Wan L, Xu S. Chlorogenic Acid Alleviates Aβ(25-35)-Induced Autophagy and Cognitive Impairment via the mTOR/TFEB Signaling Pathway. Drug design, development and therapy. 2020;14:1705-16.https://doi.org/10.2147/dddt.S235969.
  25. Fang H, Li HF, He MH, Yan JY, Yang M, Zhang FX, et al. Long non-coding RNA MALAT1 sponges microRNA-429 to regulate apoptosis of hippocampal neurons in hypoxic-ischemic brain damage by regulating WNT1. Brain research bulletin. 2019;152:1-10.https://doi.org/10.1016/j.brainresbull.2019.06.004.
آمار
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