MicroRNA-137-3p Protects PC12 Cells Against Oxidative Stress by Downregulation of Calpain-2 and nNOS

Tang, Ying; Li, Yingqin; Yu, Guangyin; Ling, Zemin; Zhong, Ke; Zilundu, Prince L. M.; Li, Wenfu; Fu, Rao; Zhou, Li-Hua

doi:10.1007/s10571-020-00908-0

Original Research
Published: 27 June 2020

MicroRNA-137-3p Protects PC12 Cells Against Oxidative Stress by Downregulation of Calpain-2 and nNOS

Ying Tang¹,
Yingqin Li²,
Guangyin Yu¹,
Zemin Ling³,
Ke Zhong¹,
Prince L. M. Zilundu¹,
Wenfu Li⁴,
Rao Fu ORCID: orcid.org/0000-0002-7551-4618⁴ &
Li-Hua Zhou⁴

Cellular and Molecular Neurobiology volume 41, pages 1373–1387 (2021)Cite this article

474 Accesses
6 Citations
Metrics details

Abstract

The imbalance between excess reactive oxygen species (ROS) generation and insufficient antioxidant defenses contribute to a range of neurodegenerative diseases. High ROS levels damage cellular macromolecules such as DNA, proteins and lipids, leading to neuron vulnerability and eventual death. However, the underlying molecular mechanism of the ROS regulation is not fully elucidated. Recently, an increasing number of studies suggest that microRNAs (miRNAs) emerge as the targets in regulating oxidative stress. We recently reported the neuroprotective effect of miR-137-3p for brachial plexus avulsion-induced motoneuron death. The present study is sought to investigate whether miR-137-3p also could protect PC12 cells against hydrogen peroxide (H₂O₂) induced neurotoxicity. By using cell viability assay, ROS assay, gene and protein expression assay, we found that PC-12 cells exposed to H₂O₂ exhibited decreased cell viability, increased expression levels of calpain-2 and neuronal nitric oxide synthase (nNOS), whereas a decreased miR-137-3p expression. Importantly, restoring the miR-137-3p levels in H₂O₂ exposure robustly inhibited the elevated nNOS, calpain-2 and ROS expression levels, which subsequently improved the cell viability. Furthermore, the suppressive effect of miR-137-3p on the elevated ROS level under oxidative stress was considerably blunted when we mutated the binding site of calpain-2 targted by miR-137-3p, suggesting the critical role of calpain-2 involving the neuroprotective effect of miR-137-3p. Collectively, these findings highlight the neuroprotective role of miR-137-3p through down-regulating calpain and NOS activity, suggesting its potential role for combating oxidative stress insults in the neurodegenerative diseases.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

Alvira D, Ferrer I, Gutierrez-Cuesta J, Garcia-Castro B, Pallas M, Camins A (2008) Activation of the calpain/cdk5/p25 pathway in the girus cinguli in Parkinson's disease. Parkinsonism Relat Disord 14(4):309–313. https://doi.org/10.1016/j.parkreldis.2007.09.005
Article PubMed Google Scholar
Araujo IM, Carvalho CM (2005) Role of nitric oxide and calpain activation in neuronal death and survival. Curr Drug Targets CNS Neurol Disord 4(4):319–324. https://doi.org/10.2174/1568007054546126
CAS Article PubMed Google Scholar
Avery SV (2011) Molecular targets of oxidative stress. Biochem J 434(2):201–210. https://doi.org/10.1042/BJ20101695
CAS Article PubMed Google Scholar
Barber SC, Shaw PJ (2010) Oxidative stress in ALS: Key role in motor neuron injury and therapeutic target. Free Radic Biol Med 48(5):629–641. https://doi.org/10.1016/j.freeradbiomed.2009.11.018
CAS Article PubMed Google Scholar
Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. https://doi.org/10.1016/j.cell.2009.01.002
CAS Article PubMed PubMed Central Google Scholar
Bartoszewski R, Sikorski AF (2019) Editorial focus: understanding off-target effects as the key to successful RNAi therapy. Cell Mol Biol Lett 24:69. https://doi.org/10.1186/s11658-019-0196-3
CAS Article PubMed PubMed Central Google Scholar
Chang H, Sheng JJ, Zhang L, Yue ZJ, Jiao B, Li JS, Yu ZB (2015) ROS-induced nuclear translocation of calpain-2 facilitates cardiomyocyte apoptosis in tail-suspended rats. J Cell Biochem 116(10):2258–2269. https://doi.org/10.1002/jcb.25176
CAS Article PubMed Google Scholar
Chen B, Zhao Q, Ni R, Tang F, Shan L, Cepinskas I, Cepinskas G, Wang W, Schiller PW, Peng T (2014) Inhibition of calpain reduces oxidative stress and attenuates endothelial dysfunction in diabetes. Cardiovasc Diabetol 13:88. https://doi.org/10.1186/1475-2840-13-88
CAS Article PubMed PubMed Central Google Scholar
Chen XH, Zhou X, Yang XY, Zhou ZB, Lu DH, Tang Y, Ling ZM, Zhou LH, Feng X (2016) Propofol protects against H₂O₂-induced oxidative injury in differentiated PC12 cells via inhibition of Ca²⁺-dependent NADPH oxidase. Cell Mol Neurobiol 36(4):541–551. https://doi.org/10.1007/s10571-015-0235-1
CAS Article PubMed Google Scholar
Cheng X, Fu R, Gao M, Liu S, Li YQ, Song FH, Bruce IC, Zhou LH, Wu W (2013) Intrathecal application of short interfering RNA knocks down c-jun expression and augments spinal motoneuron death after root avulsion in adult rats. Neuroscience 241:268–279. https://doi.org/10.1016/j.neuroscience.2013.03.006
CAS Article PubMed Google Scholar
Cheng X, Luo HX, Hou ZJ, Huang Y, Sun JB, Zhuo LH (2014) Neuronal nitric oxide synthase, as a downstream signaling molecule of c-jun, regulates the survival of differentiated PC12 cells. Mol Med Rep 10(4):1881–1886. https://doi.org/10.3892/mmr.2014.2415
CAS Article PubMed Google Scholar
Chi SW, Zang JB, Mele A, Darnell RB (2009) Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460(7254):479–486. https://doi.org/10.1038/nature08170
CAS Article PubMed PubMed Central Google Scholar
Chocry M, Leloup L, Kovacic H (2017) Reversion of resistance to oxaliplatin by inhibition of p38 MAPK in colorectal cancer cell lines: involvement of the calpain/Nox1 pathway. Oncotarget 8(61):103710–103730. https://doi.org/10.18632/oncotarget.21780
Article PubMed PubMed Central Google Scholar
Crocker SJ, Smith PD, Jackson-Lewis V, Lamba WR, Hayley SP, Grimm E, Callaghan SM, Slack RS, Melloni E, Przedborski S, Robertson GS, Anisman H, Merali Z, Park DS (2003) Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson's disease. J Neurosci 23(10):4081–4091
CAS Article Google Scholar
Curtin JF, Donovan M, Cotter TG (2002) Regulation and measurement of oxidative stress in apoptosis. J Immunol Methods 265(1–2):49–72. https://doi.org/10.1016/s0022-1759(02)00070-4
CAS Article PubMed Google Scholar
Dai J, Xu LJ, Han GD, Sun HL, Zhu GT, Jiang HT, Yu GY, Tang XM (2018) MiR-137 attenuates spinal cord injury by modulating NEUROD4 through reducing inflammation and oxidative stress. Eur Rev Med Pharmacol Sci 22(7):1884–1890
CAS PubMed Google Scholar
Davila D, Torres-Aleman I (2008) Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling. Mol Biol Cell 19(5):2014–2025. https://doi.org/10.1091/mbc.E07-08-0811
CAS Article PubMed PubMed Central Google Scholar
Dias V, Junn E, Mouradian MM (2013) The role of oxidative stress in Parkinson's disease. J Parkinsons Dis 3(4):461–491. https://doi.org/10.3233/JPD-130230
CAS Article PubMed PubMed Central Google Scholar
Dringen R (2005) Oxidative and antioxidative potential of brain microglial cells. Antioxid Redox Signal 7(9–10):1223–1233. https://doi.org/10.1089/ars.2005.7.1223
CAS Article PubMed Google Scholar
Edlund J, Fasching A, Liss P, Hansell P, Palm F (2010) The roles of NADPH-oxidase and nNOS for the increased oxidative stress and the oxygen consumption in the diabetic kidney. Diabetes Metab Res Rev 26(5):349–356. https://doi.org/10.1002/dmrr.1099
CAS Article PubMed PubMed Central Google Scholar
Enokido Y, Hatanaka H (1993) Apoptotic cell death occurs in hippocampal neurons cultured in a high oxygen atmosphere. Neuroscience 57(4):965–972. https://doi.org/10.1016/0306-4522(93)90041-d
CAS Article PubMed Google Scholar
Eruslanov E, Kusmartsev S (2010) Identification of ROS using oxidized DCFDA and flow-cytometry. Adv Protoc Oxid Stress II 594:57–72. https://doi.org/10.1007/978-1-60761-411-1_4
CAS Article Google Scholar
Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J. https://doi.org/10.1093/eurheartj/ehr304
Article PubMed Google Scholar
Gao L, Dai C, Feng Z, Zhang L, Zhang Z (2018) MiR-137 inhibited inflammatory response and apoptosis after spinal cord injury via targeting of MK2. J Cell Biochem 119(4):3280–3292. https://doi.org/10.1002/jcb.26489
CAS Article PubMed Google Scholar
Gao F, Lei J, Zhang Z, Yang Y, You H (2019) Curcumin alleviates LPS-induced inflammation and oxidative stress in mouse microglial BV2 cells by targeting miR-137-3p/NeuroD1. RSC Adv 9(66):38397–38406. https://doi.org/10.1039/c9ra07266g
CAS Article Google Scholar
Gurtan AM, Sharp PA (2013) The role of miRNAs in regulating gene expression networks. J Mol Biol 425(19):3582–3600. https://doi.org/10.1016/j.jmb.2013.03.007
CAS Article PubMed PubMed Central Google Scholar
Hara T, Mahadevan J, Kanekura K, Hara M, Lu SM, Urano F (2014) Calcium efflux from the endoplasmic reticulum leads to beta-cell death. Endocrinology 155(3):758–768. https://doi.org/10.1210/en.2013-1519
CAS Article PubMed Google Scholar
Hong ZW, Tian YJ, Yuan YB, Qi MW, Li YC, Di YM, Chen L, Chen L (2016) Enhanced oxidative stress is responsible for TRPV4-induced neurotoxicity. Front Cell Neurosci 10:232. https://doi.org/10.3389/fncel.2016.00232
CAS Article PubMed PubMed Central Google Scholar
Huang CJ, Gurlo T, Haataja L, Costes S, Daval M, Ryazantsev S, Wu XJ, Butler AE, Butler PC (2010) Calcium-activated calpain-2 is a mediator of beta cell dysfunction and apoptosis in type 2 diabetes. J Biol Chem 285(1):339–348. https://doi.org/10.1074/jbc.M109.024190
CAS Article PubMed Google Scholar
Huang WJ, Zhang X, Chen WW (2016) Role of oxidative stress in Alzheimer's disease. Biomed Rep 4(5):519–522. https://doi.org/10.3892/br.2016.630
CAS Article PubMed PubMed Central Google Scholar
Junn E, Mouradian MM (2012) MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol Ther 133(2):142–150. https://doi.org/10.1016/j.pharmthera.2011.10.002
CAS Article PubMed Google Scholar
Kannan K, Jain SK (2000) Oxidative stress and apoptosis. Pathophysiology 7(3):153–163. https://doi.org/10.1016/s0928-4680(00)00053-5
CAS Article PubMed Google Scholar
Kar R, Kellogg DL, Roman LJ (2015) Oxidative stress induces phosphorylation of neuronal NOS in cardiomyocytes through AMP-activated protein kinase (AMPK). Biochem Biophys Res Commun 459(3):393–397. https://doi.org/10.1016/j.bbrc.2015.02.113
CAS Article PubMed PubMed Central Google Scholar
Khan M, Dhammu TS, Matsuda F, Annamalai B, Dhindsa TS, Singh I, Singh AK (2016) Targeting the nNOS/peroxynitrite/calpain system to confer neuroprotection and aid functional recovery in a mouse model of TBI. Brain Res 1630:159–170. https://doi.org/10.1016/j.brainres.2015.11.015
CAS Article PubMed Google Scholar
Kong LF, Wei QW, Fedail JS, Shi FX, Nagaoka K, Watanabe G (2015) Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats. J Reprod Dev 61(3):219–227. https://doi.org/10.1262/jrd.2014-129
Article PubMed PubMed Central Google Scholar
Kopincova J, Puzserova A, Bernatova I (2011) Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide. Interdiscip Toxicol 4(2):63–68. https://doi.org/10.2478/v10102-011-0012-z
CAS Article PubMed PubMed Central Google Scholar
Lai X, Eberhardt M, Schmitz U, Vera J (2019) Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer. Nucleic Acids Res 47(15):7753–7766. https://doi.org/10.1093/nar/gkz638
CAS Article PubMed PubMed Central Google Scholar
Li R, Yin F, Guo YY, Zhao KC, Ruan Q, Qi YM (2017) Knockdown of ANRIL aggravates H₂O₂-induced injury in PC-12 cells by targeting microRNA-125a. Biomed Pharmacother 92:952–961. https://doi.org/10.1016/j.biopha.2017.05.122
CAS Article PubMed Google Scholar
Luo P, Chen T, Zhao YB, Xu HX, Huo K, Zhao MM, Yang YF, Fei Z (2012) Protective effect of Homer 1a against hydrogen peroxide-induced oxidative stress in PC12 cells. Free Radical Res 46(6):766–776. https://doi.org/10.3109/10715762.2012.678340
CAS Article Google Scholar
Mahmoudi E, Cairns MJ (2017) MiR-137: an important player in neural development and neoplastic transformation. Mol Psychiatry 22(1):44–55. https://doi.org/10.1038/mp.2016.150
CAS Article PubMed Google Scholar
Mesenge C, Verrecchia C, Allix M, Boulu RR, Plotkine M (1996) Reduction of the neurological deficit in mice with traumatic brain injury by nitric oxide synthase inhibitors. J Neurotrauma 13(4):209–214
CAS Article Google Scholar
Momeni HR (2011) Role of calpain in apoptosis. Cell J 13(2):65–72
CAS PubMed PubMed Central Google Scholar
Nathan C (1997) Inducible nitric oxide synthase: what difference does it make? J Clin Investig 100(10):2417–2423. https://doi.org/10.1172/JCI119782
CAS Article PubMed PubMed Central Google Scholar
Nixon RA, Saito KI, Grynspan F, Griffin WR, Katayama S, Honda T, Mohan PS, Shea TB, Beermann M (1994) Calcium-activated neutral proteinase (calpain) system in aging and Alzheimer's disease. Ann N Y Acad Sci 747:77–91. https://doi.org/10.1111/j.1749-6632.1994.tb44402.x
CAS Article PubMed Google Scholar
Ray SK, Fidan M, Nowak MW, Wilford GG, Hogan EL, Banik NL (2000) Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells. Brain Res 852(2):326–334. https://doi.org/10.1016/S0006-8993(99)02148-4
CAS Article PubMed Google Scholar
Saatman KE, Creed J, Raghupathi R (2010) Calpain as a therapeutic target in traumatic brain injury. Neurotherapeutics 7(1):31–42. https://doi.org/10.1016/j.nurt.2009.11.002
CAS Article PubMed PubMed Central Google Scholar
Saito K, Elce JS, Hamos JE, Nixon RA (1993) Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration. Proc Natl Acad Sci USA 90(7):2628–2632. https://doi.org/10.1073/pnas.90.7.2628
CAS Article PubMed PubMed Central Google Scholar
Salim S (2017) Oxidative stress and the central nervous system. J Pharmacol Exp Ther 360(1):201–205. https://doi.org/10.1124/jpet.116.237503
CAS Article PubMed PubMed Central Google Scholar
Shafi G, Aliya N, Munshi A (2010) MicroRNA signatures in neurological disorders. Can J Neurol Sci 37(2):177–185. https://doi.org/10.1017/s0317167100009902
Article PubMed Google Scholar
Simonian NA, Coyle JT (1996) Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 36:83–106. https://doi.org/10.1146/annurev.pa.36.040196.000503
CAS Article PubMed Google Scholar
Slivka A, Mytilineou C, Cohen G (1987a) Histochemical evaluation of glutathione in brain. Brain Res 409(2):275–284. https://doi.org/10.1016/0006-8993(87)90712-8
CAS Article PubMed Google Scholar
Slivka A, Spina MB, Cohen G (1987b) Reduced and oxidized glutathione in human and monkey brain. Neurosci Lett 74(1):112–118. https://doi.org/10.1016/0304-3940(87)90061-9
CAS Article PubMed Google Scholar
Su YR, Wang J, Wu JJ, Chen Y, Jiang YP (2007) Overexpression of lentivirus-mediated glial cell line-derived neurotrophic factor in bone marrow stromal cells and its neuroprotection for the PC12 cells damaged by lactacystin. Neurosci Bull 23(2):67–74. https://doi.org/10.1007/s12264-007-0010-5
CAS Article PubMed Google Scholar
Suzuki K (1991) Nomenclature of calcium dependent proteinase. Biomed Biochim Acta 50(4–6):483–484
CAS PubMed Google Scholar
Tang Y, Fu R, Ling ZM, Liu LL, Yu GY, Li W, Fang XY, Zhu Z, Wu WT, Zhou LH (2018) MiR-137-3p rescue motoneuron death by targeting calpain-2. Nitric Oxide Biol Chem 74:74–85. https://doi.org/10.1016/j.niox.2018.01.008
CAS Article Google Scholar
Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7(1):65–74. https://doi.org/10.2174/157015909787602823
CAS Article PubMed PubMed Central Google Scholar
Vosler PS, Brennan CS, Chen J (2008) Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. Mol Neurobiol 38(1):78–100. https://doi.org/10.1007/s12035-008-8036-x
CAS Article PubMed PubMed Central Google Scholar
Wang Z, Liu Y, Han N, Chen X, Yu W, Zhang W, Zou F (2010) Profiles of oxidative stress-related microRNA and mRNA expression in auditory cells. Brain Res 1346:14–25. https://doi.org/10.1016/j.brainres.2010.05.059
CAS Article PubMed Google Scholar
Wang S, Guo C, Yu M, Ning X, Yan B, Zhao J, Yang A, Yan H (2018) Identification of H₂O₂ induced oxidative stress associated microRNAs in HLE-B3 cells and their clinical relevance to the progression of age-related nuclear cataract. BMC Ophthalmol 18(1):93. https://doi.org/10.1186/s12886-018-0766-6
CAS Article PubMed PubMed Central Google Scholar
Wei G, Dawson VL, Zweier JL (1999) Role of neuronal and endothelial nitric oxide synthase in nitric oxide generation in the brain following cerebral ischemia. Biochim Biophys Acta 1455(1):23–34. https://doi.org/10.1016/s0925-4439(99)00051-4
CAS Article PubMed Google Scholar
Wingrave JM, Schaecher KE, Sribnick EA, Wilford GG, Ray SK, Hazen-Martin DJ, Hogan EL, Banik NL (2003) Early induction of secondary injury factors causing activation of calpain and mitochondria-mediated neuronal apoptosis following spinal cord injury in rats. J Neurosci Res 73(1):95–104. https://doi.org/10.1002/jnr.10607
CAS Article PubMed Google Scholar
Wu W (1993) Expression of nitric-oxide synthase (NOS) in injured CNS neurons as shown by NADPH diaphorase histochemistry. Exp Neurol 120(2):153–159. https://doi.org/10.1006/exnr.1993.1050
CAS Article PubMed Google Scholar
Wu W, Li L (1993) Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion. Neurosci Lett 153(2):121–124. https://doi.org/10.1016/0304-3940(93)90303-3
CAS Article PubMed Google Scholar
Xu W, Chi L, Xu R, Ke Y, Luo C, Cai J, Qiu M, Gozal D, Liu R (2005) Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. Spinal Cord 43(4):204–213. https://doi.org/10.1038/sj.sc.3101674
CAS Article PubMed Google Scholar
Yun HY, Dawson VL, Dawson TM (1997) Nitric oxide in health and disease of the nervous system. Mol Psychiatry 2(4):300–310. https://doi.org/10.1038/sj.mp.4000272
CAS Article PubMed Google Scholar
Zeevalk GD, Bernard LP, Nicklas WJ (1998) Role of oxidative stress and the glutathione system in loss of dopamine neurons due to impairment of energy metabolism. J Neurochem 70(4):1421–1430. https://doi.org/10.1046/j.1471-4159.1998.70041421.x
CAS Article PubMed Google Scholar
Zhu H, Bhattacharyya B, Lin H, Gomez CM (2013) Skeletal muscle calpain acts through nitric oxide and neural miRNAs to regulate acetylcholine release in motor nerve terminals. J Neurosci 33(17):7308–7324. https://doi.org/10.1523/JNEUROSCI.0224-13.2013
CAS Article PubMed PubMed Central Google Scholar

Download references

Funding

This work was supported by research grants from the National Natural Science Foundation of China (81771325) and Sun Yat-sen University Research Startup Foundation (59000-18841219).

Author information

Affiliations

Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
Ying Tang, Guangyin Yu, Ke Zhong & Prince L. M. Zilundu
Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 51900, Guangdong, China
Yingqin Li
Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
Zemin Ling
Department of Anatomy, School of Medicine, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
Wenfu Li, Rao Fu & Li-Hua Zhou

Authors

Ying Tang
View author publications
You can also search for this author in PubMed Google Scholar
Yingqin Li
View author publications
You can also search for this author in PubMed Google Scholar
Guangyin Yu
View author publications
You can also search for this author in PubMed Google Scholar
Zemin Ling
View author publications
You can also search for this author in PubMed Google Scholar
Ke Zhong
View author publications
You can also search for this author in PubMed Google Scholar
Prince L. M. Zilundu
View author publications
You can also search for this author in PubMed Google Scholar
Wenfu Li
View author publications
You can also search for this author in PubMed Google Scholar
Rao Fu
View author publications
You can also search for this author in PubMed Google Scholar
Li-Hua Zhou
View author publications
You can also search for this author in PubMed Google Scholar

Contributions

YT and RF performed the experiment, wrote the manuscript, acquired the data, and created the figures. YQL,GYY,ZML,KZ, PLMZ, and WFL performed experiments and data analysis. RF and LHZ designed the study and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Rao Fu or Li-Hua Zhou.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tang, Y., Li, Y., Yu, G. et al. MicroRNA-137-3p Protects PC12 Cells Against Oxidative Stress by Downregulation of Calpain-2 and nNOS. Cell Mol Neurobiol 41, 1373–1387 (2021). https://doi.org/10.1007/s10571-020-00908-0

Download citation

Received: 04 March 2020
Accepted: 19 June 2020
Published: 27 June 2020
Issue Date: August 2021
DOI: https://doi.org/10.1007/s10571-020-00908-0

Keywords

miR-137-3p
Calpain-2
Neuronal nitric oxide synthase
Oxidative stress
Reactive oxygen species