Neuroprotective Effects of Exogenous Activin A on Oxygen-Glucose Deprivation in PC12 Cells

Springer Science and Business Media LLC - Tập 17 Số 1 - Trang 315-327
Jinting He1, Jing Mang1, Chunli Mei2,1, Le Yang3, Jiaoqi Wang1, Ying Xing1, Hong Yang1, Zhongxin Xu1
1Department of Neurology, China-Japan Friendship Hospital, Jilin University, Changchun 130012, China
2College of Nursing, Beihua University, Jilin 132013, China
3People's Hospital of Jilin Province, Changchun 130021, China

Tóm tắt

Ischemic cerebrovascular disease is one of the most common causes of death in the World. Exogenous activin A (ActA) protects neurons against toxicity and plays a central role in regulating the brain’s response to injury. In the present study, we investigated the mechanisms involved in the neuroprotective effects of ActA in a model of hypoxic-ischemic brain disease. We found that ActA could effectively increase the survival rate of PC12 cells and relieve oxygen-glucose deprivation (OGD) damage. To clarify the neuroprotective mechanisms of ActA, the effects of ActA on the ActA/Smad pathway and on the up-regulation of inducible nitric oxide synthase (NOS) and superoxide dismutase (SOD) were investigated using OGD in PC12 cells. The results showed that ActA could increase the expression of activin receptor IIA (ActRIIA), Smad3 and Smad4 and that 50 ng/mL and 100 ng/mL of ActA could reduce NO levels and increase SOD activity by 78.9% and 79.9%, respectively. These results suggested that the neuroprotective effects of ActA in ischemia could be related to the activation of the ActA/Smad signaling pathway and to its anti-oxidant activities.

Từ khóa


Tài liệu tham khảo

Paeme, 2011, Mathematical multi-scale model of the cardiovascular system including mitral valve dynamics. Application to ischemic mitral insufficiency, Biomed. Eng. Online, 10, 86, 10.1186/1475-925X-10-86

Barbarash, 2011, Prevalence and clinical significance of multifocal atherosclerosis in patients with ischemic heart disease, Kardiologiia, 51, 66

Meschia, 2011, Siblings with ischemic stroke study: Results of a genome-wide scan for stroke loci, Stroke, 42, 2726, 10.1161/STROKEAHA.111.620484

Foster, 2011, Ischemic preconditioning of the lower extremity attenuates the normal hypoxic increase in pulmonary artery systolic pressure, Respir. Physiol. Neurobiol., 179, 248, 10.1016/j.resp.2011.09.001

Ageta, 2011, Multifunctional roles of activins in the brain, Vitam. Horm., 85, 185, 10.1016/B978-0-12-385961-7.00009-3

Deli, 2008, Activins and activin antagonists in hepatocellular carcinoma, World J. Gastroenterol., 14, 1699, 10.3748/wjg.14.1699

Kang, 2011, Activins and cell migration, Vitam. Horm., 85, 129, 10.1016/B978-0-12-385961-7.00007-X

Munz, 2001, The roles of activins in repair processes of the skin and the brain, Mol. Cell. Endocrinol., 180, 169, 10.1016/S0303-7207(01)00514-7

Florio, 2007, Activin A in brain injury, Adv. Clin. Chem., 43, 117, 10.1016/S0065-2423(06)43004-3

Mukerji, 2009, Delayed activin A administration attenuates tissue death after transient focal cerebral ischemia and is associated with decreased stress-responsive kinase activation, J. Neurochem., 111, 1138, 10.1111/j.1471-4159.2009.06406.x

Liu, 2010, Neuroprotective effect of osthole on MPP+-induced cytotoxicity in PC12 cells via inhibition of mitochondrial dysfunction and ROS production, Neurochem. Int., 57, 206, 10.1016/j.neuint.2010.05.011

Chen, 2011, Neuroprotective effect of osthole against oxygen and glucose deprivation in rat cortical neurons: Involvement of mitogen-activated protein kinase pathway, Neuroscience, 183, 203, 10.1016/j.neuroscience.2011.03.038

Winkler, 2011, Lack of Smad or Notch leads to a fatal game of brain pericyte hopscotch, Dev. Cell, 20, 279, 10.1016/j.devcel.2011.03.002

Phillips, 2006, Activin a release into cerebrospinal fluid in a subset of patients with severe traumatic brain injury, J. Neurotraum., 23, 1283, 10.1089/neu.2006.23.1283

Wu, 1999, Expression of the activin axis and neuronal rescue effects of recombinant activin A following hypoxic-ischemic brain injury in the infant rat, Brain Res., 835, 369, 10.1016/S0006-8993(99)01638-8

Tong, 2009, Epigallocatechin gallate induces apoptosis in human hepatocellular carcinoma HepG2 cells via TGF/Smad signaling pathway, Zhonghua Zhong Liu Za Zhi, 31, 646

Yao, 2008, The role of the TGF/Smad signaling pathway in peritoneal fibrosis induced by peritoneal dialysis solutions, Nephron. Exp. Nephrol., 109, e71, 10.1159/000142529

Leonardi, 2011, Transforming growth factor-beta/Smad—Signalling pathway and conjunctival remodelling in vernal keratoconjunctivitis, Clin. Exp. Allergy, 41, 52, 10.1111/j.1365-2222.2010.03626.x

Nakamura, 2011, Smad ubiquitination regulatory factor-2 in progressive supranuclear palsy, Neuropathol. Appl. Neurobiol., 37, 307, 10.1111/j.1365-2990.2010.01120.x

Sachdev, 2011, High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury, J. Vasc. Surg., 55, 180, 10.1016/j.jvs.2011.07.072

Templin, 2010, Stem and progenitor cell-based therapy approaches: Current developments on treatment of acute myocardial infarction and chronic ischemic cardiomyopathy, Herz, 35, 445, 10.1007/s00059-010-3397-0

Schwarz, 2011, Platelet glycoprotein Ibalpha is an important mediator of ischemic stroke in mice, Exp. Transl. Stroke Med., 3, 9, 10.1186/2040-7378-3-9

Shudo, 2011, Establishing new porcine ischemic cardiomyopathy model by transcatheter ischemia-reperfusion of the entire left coronary artery system for preclinical experimental studies, Transplantation, 92, e34, 10.1097/TP.0b013e31822d875c

Park, 2011, Microtubule-associated protein 2, an early blood marker of ischemic brain injury, J. Neurosci. Res., 90, 461, 10.1002/jnr.22769

Li, 2009, Oxygen-glucose deprivation activates 5-lipoxygenase mediated by oxidative stress through the p38 mitogen-activated protein kinase pathway in PC12 cells, J. Neurosci. Res., 87, 991, 10.1002/jnr.21913

Longxi, 2011, Expression of p53 in the effects of artesunate on induction of apoptosis and inhibition of proliferation in rat primary hepatic stellate cells, PLoS One, 6, e26500, 10.1371/journal.pone.0026500

Rao, 2011, In vitro and in vivo antioxidant properties of the plant-based supplement greens+, Int. J. Mol. Sci., 12, 4896, 10.3390/ijms12084896

Han, 2009, Antiproliferation and apoptosis induced by tamoxifen in human bile duct carcinoma QBC939 cells via upregulated p53 expression, Biochem. Biophys. Res. Commun., 385, 251, 10.1016/j.bbrc.2009.05.059

Tara, 2011, Novel approach to ischemic skin ulcer in systemic lupus erythematosus: Therapeutic angiogenesis by controlled-release basic fibroblast growth factor, Geriatr. Gerontol. Int., 11, 527, 10.1111/j.1447-0594.2011.00695.x

Pieri, 2011, Stratification with CHA2DS2-VASc score is better than CHADS2 score in reducing ischemic stroke risk in patients with atrial fibrillation, Int. J. Stroke, 6, 466, 10.1111/j.1747-4949.2011.00650.x

Peng, 2011, Standard medical management in secondary prevention of ischemic stroke in China (SMART), Int. J. Stroke, 6, 461, 10.1111/j.1747-4949.2011.00648.x

Kim, 2011, Hemorrhagic transformation of ischemic stroke: Severe complications of prosthetic valve endocarditis, Korean Circ. J., 41, 490, 10.4070/kcj.2011.41.8.490

Zubkiewicz, 2008, Impact of nebivolol on levels of serum nitric oxide, plasma von Willebrand factor and exercise stress testing parameters in hypertensive and ischemic heart disease patients, Cardiol. J., 15, 162