{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:50:05Z","timestamp":1790700605088,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clinical and experimental data assumed a neuroprotective effect of the calcium channel blocker nimodipine. However, it has not been proven which neuronal or glial cell types are affected by nimodipine and which mechanisms underlie these neuroprotective effects. Therefore, the aim of this study was to investigate the influence of nimodipine treatment on the in vitro neurotoxicity of different cell types in various stress models and to identify the associated molecular mechanisms. Therefore, cell lines from Schwann cells, neuronal cells and astrocytes were pretreated for 24 h with nimodipine and incubated under stress conditions such as osmotic, oxidative and heat stress. The cytotoxicity was measured via the lactate dehydrogenase (LDH) activity of cell culture supernatant. As a result, the nimodipine treatment led to a statistically significantly reduced cytotoxicity in Schwann cells and neurons during osmotic (p \u2264 0.01), oxidative (p \u2264 0.001) and heat stress (p \u2264 0.05), when compared to the vehicle. The cytotoxicity of astrocytes was nimodipine-dependently reduced during osmotic (p \u2264 0.01), oxidative (p \u2264 0.001) and heat stress (not significant). Moreover, a decreased caspase activity as well as an increased proteinkinase B (AKT) and cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation could be observed after the nimodipine treatment under different stress conditions. These results demonstrate a cell type-independent neuroprotective effect of the prophylactic nimodipine treatment, which is associated with the prevention of stress-dependent apoptosis through the activation of CREB and AKT signaling pathways and the reduction of caspase 3 activity.<\/jats:p>","DOI":"10.3390\/ijms20184578","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T03:31:46Z","timestamp":1568691106000},"page":"4578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Nimodipine-Dependent Protection of Schwann Cells, Astrocytes and Neuronal Cells from Osmotic, Oxidative and Heat Stress Is Associated with the Activation of AKT and CREB"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4581-5185","authenticated-orcid":false,"given":"Sandra","family":"Leisz","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2856-6500","authenticated-orcid":false,"given":"Sebastian","family":"Simmermacher","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Prell","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Scheller","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s11940-005-0019-x","article-title":"Cerebral Vasospasm in Subarachnoid Hemorrhage","volume":"7","author":"Rabinstein","year":"2005","journal-title":"Curr. Treat Options Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dorhout Mees, S.M., Rinkel, G.J., Feigin, V.L., Algra, A., van den Bergh, W.M., Vermeulen, M., and van Gijn, J. (2007). Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD000277.pub3"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S1474-4422(10)70087-9","article-title":"Multidisciplinary management and emerging therapeutic strategies in aneurysmal subarachnoid haemorrhage","volume":"9","author":"Rabinstein","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jcms.2011.07.016","article-title":"Nimodipine promotes regeneration of peripheral facial nerve function after traumatic injury following maxillofacial surgery: An off label pilot-study","volume":"40","author":"Scheller","year":"2012","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1055\/s-0032-1313724","article-title":"Prophylactic intravenous nimodipine treatment in skull base surgery: Pharmacokinetic aspects","volume":"73","author":"Scheller","year":"2012","journal-title":"J. Neurol. Surg. A Cent. Eur. Neurosurg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/mus.24462","article-title":"Nimodipine for peripheral nerve recovery after maxillofacial and vestibular schwannoma surgery","volume":"50","author":"Scheller","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1177\/000348940711600811","article-title":"Nimodipine improves reinnervation and neuromuscular function after injury to the recurrent laryngeal nerve in the rat","volume":"116","author":"Hydman","year":"2007","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1097\/01.mlg.0000177034.51559.50","article-title":"Nimodipine and microsurgery induced recovery of the vocal cord after recurrent laryngeal nerve resection","volume":"115","author":"Mattsson","year":"2005","journal-title":"Laryngoscope"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1007\/s00268-017-4235-9","article-title":"Recovery of Voice After Reconstruction of the Recurrent Laryngeal Nerve and Adjuvant Nimodipine","volume":"42","author":"Mattsson","year":"2018","journal-title":"World J. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.3390\/molecules20011003","article-title":"Neuroprotective and neuroregenerative effects of nimodipine in a model system of neuronal differentiation and neurite outgrowth","volume":"20","author":"Bork","year":"2015","journal-title":"Molecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18453","DOI":"10.3390\/ijms151018453","article-title":"Investigation of the neuroprotective impact of nimodipine on Neuro2a cells by means of a surgery-like stress model","volume":"15","author":"Herzfeld","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Herzfeld, E., Speh, L., Strauss, C., and Scheller, C. (2017). Nimodipine but Not Nifedipine Promotes Expression of Fatty Acid 2-Hydroxylase in a Surgical Stress Model Based on Neuro2a Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050964"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10571-014-0110-5","article-title":"Nimodipine activates TrkB neurotrophin receptors and induces neuroplastic and neuroprotective signaling events in the mouse hippocampus and prefrontal cortex","volume":"35","author":"Matsui","year":"2015","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/2110-5820-1-12","article-title":"Pharmacological treatment of delayed cerebral ischemia and vasospasm in subarachnoid hemorrhage","volume":"1","author":"Hantson","year":"2011","journal-title":"Ann. Intensive Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jns.2018.02.039","article-title":"Novel management strategies for medically-refractory vasospasm following aneurysmal subarachnoid hemorrhage","volume":"390","author":"Amuluru","year":"2018","journal-title":"J. Neurol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1212\/WNL.50.4.876","article-title":"Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: A systematic review","volume":"50","author":"Feigin","year":"1998","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1227\/01.neu.0000279728.98273.51","article-title":"The influence of prophylactic vasoactive treatment on cochlear and facial nerve functions after vestibular schwannoma surgery: A prospective and open-label randomized pilot study","volume":"61","author":"Scheller","year":"2007","journal-title":"Neurosurgery"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3171\/2015.1.JNS142001","article-title":"Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: A randomized multicenter Phase III trial","volume":"124","author":"Scheller","year":"2016","journal-title":"J. Neurosurg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.3171\/2016.8.JNS16626","article-title":"Prophylactic nimodipine treatment and improvement in hearing outcome after vestibular schwannoma surgery: A combined analysis of a randomized, multicenter, Phase III trial and its pilot study","volume":"127","author":"Scheller","year":"2017","journal-title":"J. Neurosurg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1161\/01.STR.32.2.461","article-title":"Very Early Nimodipine Use in Stroke (VENUS): A randomized, double-blind, placebo-controlled trial","volume":"32","author":"Horn","year":"2001","journal-title":"Stroke"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3171\/jns.1996.84.3.0405","article-title":"Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: A metaanalysis","volume":"84","author":"Barker","year":"1996","journal-title":"J. Neurosurg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1136\/bmj.298.6674.636","article-title":"Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial","volume":"298","author":"Pickard","year":"1989","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"760","DOI":"10.3171\/jns.1999.90.4.0760","article-title":"Nimodipine-induced improved survival rate of facial motor neurons following intracranial transection of the facial nerve in the adult rat","volume":"90","author":"Mattsson","year":"1999","journal-title":"J. Neurosurg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/cne.1273","article-title":"Nimodipine promotes regeneration and functional recovery after intracranial facial nerve crush","volume":"437","author":"Mattsson","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Li, Y., Bao, Y., Yin, C., Xin, X., Guo, Y., Gao, F., Huo, S., Wang, X., and Wang, Q. (2018). Pretreatment with nimodipine reduces incidence of POCD by decreasing calcineurin mediated hippocampal neuroapoptosis in aged rats. BMC Anesthesiol., 18.","DOI":"10.1186\/s12871-018-0501-0"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1080\/02844310801924266","article-title":"Thermal effect of illumination on microsurgical transfer of free flaps: Experimental study and clinical implications","volume":"42","author":"Kurita","year":"2008","journal-title":"Scand. J. Plast. Reconstr. Surg. Hand Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s12263-009-0159-9","article-title":"Ethanol-induced oxidative stress: Basic knowledge","volume":"5","author":"Comporti","year":"2010","journal-title":"Genes Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jneuroim.2010.05.024","article-title":"Stimulus-dependent requirement of ion channels for microglial NADPH oxidase-mediated production of reactive oxygen species","volume":"225","author":"Schilling","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1021\/acschemneuro.6b00042","article-title":"The Immune System and Neuroinflammation as Potential Sources of Blood-Based Biomarkers for Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Huntington\u2019s Disease","volume":"7","author":"Clark","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.pediatrneurol.2019.03.018","article-title":"Osmotic Demyelination Syndrome in Children","volume":"97","author":"Bansal","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1681\/ASN.2016050509","article-title":"Osmotic Stress-Induced Defective Glial Proteostasis Contributes to Brain Demyelination after Hyponatremia Treatment","volume":"28","author":"Couturier","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E3295","DOI":"10.1073\/pnas.1620052114","article-title":"Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis","volume":"114","author":"Schampel","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ingwersen, J., De Santi, L., Wingerath, B., Graf, J., Koop, B., Schneider, R., Hecker, C., Schr\u00f6ter, F., Bayer, M., and Engelke, A.D. (2018). Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis. J. Neurochem.","DOI":"10.1111\/jnc.14324"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1111\/j.1476-5381.2012.02112.x","article-title":"Nimodipine inhibits IL-1\u03b2 release stimulated by amyloid \u03b2 from microglia","volume":"167","author":"Sanz","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.neuint.2016.07.003","article-title":"Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice","volume":"99","author":"Singh","year":"2016","journal-title":"Neurochem. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2217\/nnm-2016-0267","article-title":"Combining nanoscale magnetic nimodipine liposomes with magnetic resonance image for Parkinson\u2019s disease targeting therapy","volume":"12","author":"Ji","year":"2017","journal-title":"Nanomedicine (Lond.)"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-3-540-69185-3_2","article-title":"Proteolytic targets in cell death","volume":"24","author":"Watters","year":"1998","journal-title":"Results Probl. Cell. Differ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1126\/science.278.5336.294","article-title":"Caspase-3-generated fragment of gelsolin: Effector of morphological change in apoptosis","volume":"278","author":"Kothakota","year":"1997","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15540","DOI":"10.1074\/jbc.273.25.15540","article-title":"Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis","volume":"273","author":"Ng","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9357","DOI":"10.1074\/jbc.273.16.9357","article-title":"Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis","volume":"273","author":"Sprengart","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0167-4838(99)00281-2","article-title":"Caspases\u2014Controlling intracellular signals by protease zymogen activation","volume":"1477","author":"Stennicke","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1126\/science.275.5300.661","article-title":"Regulation of neuronal survival by the serine-threonine protein kinase Akt","volume":"275","author":"Dudek","year":"1997","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0092-8674(00)81883-8","article-title":"PI3K: Downstream AKTion blocks apoptosis","volume":"88","author":"Franke","year":"1997","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1128\/MCB.17.3.1595","article-title":"Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt","volume":"17","author":"Kulik","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.neuint.2006.10.010","article-title":"Implication of PTEN in production of reactive oxygen species and neuronal death in in vitro models of stroke and Parkinson\u2019s disease","volume":"50","author":"Zhu","year":"2007","journal-title":"Neurochem. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.neuint.2012.10.014","article-title":"Retinoic acid protects against proteasome inhibition associated cell death in SH-SY5Y cells via the AKT pathway","volume":"62","author":"Cheng","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11845","DOI":"10.1074\/jbc.M900639200","article-title":"Regulator of calcineurin (RCAN1-1L) is deficient in Huntington disease and protective against mutant huntingtin toxicity in vitro","volume":"284","author":"Ermak","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neulet.2014.02.039","article-title":"PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury","volume":"573","author":"Walker","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"32377","DOI":"10.1074\/jbc.273.49.32377","article-title":"CREB is a regulatory target for the protein kinase Akt\/PKB","volume":"273","author":"Du","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"35454","DOI":"10.18632\/oncotarget.7721","article-title":"Control of CREB expression in tumors: From molecular mechanisms and signal transduction pathways to therapeutic target","volume":"7","author":"Steven","year":"2016","journal-title":"Oncotarget"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11010-016-2858-z","article-title":"Oxidative stress-induced CREB upregulation promotes DNA damage repair prior to neuronal cell death protection","volume":"425","author":"Pregi","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0166-2236(99)01500-3","article-title":"Is CREB a key to neuronal survival?","volume":"23","author":"Walton","year":"2000","journal-title":"Trends Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/embor.2011.151","article-title":"CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability","volume":"12","author":"Noriega","year":"2011","journal-title":"EMBO Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Martins, I.J. (2018). Heat Shock Gene Inactivation and Protein Aggregation with Links to Chronic Diseases. Diseases, 6.","DOI":"10.3390\/diseases6020039"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1161\/CIRCRESAHA.113.300536","article-title":"Regulation of Akt signaling by sirtuins: Its implication in cardiac hypertrophy and aging","volume":"114","author":"Pillai","year":"2014","journal-title":"Circ. Res."},{"key":"ref_56","first-page":"409P","article-title":"The cellular mechanism of action of nimodipine (BAY e 9736), a new calcium antagonist [proceedings]","volume":"67","author":"Towart","year":"1979","journal-title":"Br. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1210\/endo-122-6-2764","article-title":"Potassium depolarization elevates cytosolic free calcium concentration in rat anterior pituitary cells through 1,4-dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels","volume":"122","author":"Meier","year":"1988","journal-title":"Endocrinology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.ijdevneu.2012.05.007","article-title":"Neuroprotective effects of nimodipine and nifedipine in the NGF-differentiated PC12 cells exposed to oxygen-glucose deprivation or trophic withdrawal","volume":"30","author":"Lecht","year":"2012","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"24320","DOI":"10.1074\/jbc.M111.334425","article-title":"HER-2\/neu-mediated down-regulation of biglycan associated with altered growth properties","volume":"287","author":"Recktenwald","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4578\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:20:41Z","timestamp":1760188841000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,16]]},"references-count":60,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijms20184578"],"URL":"https:\/\/doi.org\/10.3390\/ijms20184578","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,16]]}}}