Neuronic autophagy contributes to p-connexin 43 degradation in hippocampal astrocytes following traumatic brain injury in rats

Sun,Li  Qian; Gao,Jun  Ling; Cui,Ying; Zhao,Man  Man; Jing,Xiao  Bin; Li,Ran; Tian,Yan  Xia; Cui,Jian  Zhong; Wu,Zhong-Xue

doi:10.3892/mmr.2015.3264

Neuronic autophagy contributes to p-connexin 43 degradation in hippocampal astrocytes following traumatic brain injury in rats

Authors:
- Li Qian Sun
- Jun Ling Gao
- Ying Cui
- Man Man Zhao
- Xiao Bin Jing
- Ran Li
- Yan Xia Tian
- Jian Zhong Cui
- Zhong-Xue Wu
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Affiliations: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Histology and Embryology, School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China, Department of Ophthalmology, Tangshan Ophthalmology Hospital, Tangshan, Hebei 063000, P.R. China, Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China
Published online on: January 27, 2015 https://doi.org/10.3892/mmr.2015.3264
Pages: 4419-4423

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Abstract

Connexins, gap junction proteins, have short half‑lives of only a few hours; therefore, degradation of these proteins can rapidly modulate their function. Autophagy is a type of degradation pathway that has been implicated in several diseases and was reported to be induced following traumatic brain injury (TBI). The aim of the present study was to investigate the involvement of neuronic autophagy in proteolysis of phosphorylated connexin 43 (p‑Cx43) in hippocampal astrocytes following TBI in rats. Western blot analysis and immunofluorescence showed a TBI‑induced increase in levels of astrocytic p‑Cx43 following treatment with 3‑methyladenine, an inhibitor of autophagy, in the hippocampus. Internalized gap junctions were observed in the neuronic cytoplasm using transmission electron microscopy. These results demonstrated that neuronic autophagy may regulate cellular levels of p‑Cx43 in hippocampal astrocytes following TBI. This therefore indicated that the persistence of p‑Cx43 accumulation was due to insufficient degradation capacity of constitutive autophagy.

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1	Reggiori F and Klionsky DJ: Autophagosomes: biogenesis from scratch? Curr Opin Cell Biol. 17:415–422. 2005. View Article : Google Scholar : PubMed/NCBI
2	Pozuelo-Rubio M: Regulation of autophagic activity by 14-3-3ζ proteins associated with class III phosphatidylinositol-3-kinase. Cell Death Differ. 18:479–492. 2011. View Article : Google Scholar :
3	Zheng YT, Shahnazari S, Brech A, Lamark T, Johansen T and Brumell JH: The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol. 183:5909–5916. 2009. View Article : Google Scholar : PubMed/NCBI
4	De Bock M, Kerrebrouck M, Wang N and Leybaert L: Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system? Front Pharmacol. 4:1202013. View Article : Google Scholar : PubMed/NCBI
5	De Maio A, Vega VL and Contreras JE: Gap junctions, homeostasis, and injury. J Cell Physiol. 191:269–82. 2002. View Article : Google Scholar : PubMed/NCBI
6	Rash JE, Yasumura T, Dudek FE and Nagy JI: Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons. J Neurosci. 21:1983–2000. 2001.PubMed/NCBI
7	Cottrell GT, Lin R, Warn-Cramer BJ, Lau AF and Burt JM: Mechanism of v-Src-and mitogen-activated protein kinase-induced reduction of gap junction communication. Am J Physiol Cell Physiol. 284:C511–C520. 2003. View Article : Google Scholar
8	Lichtenstein A, Minogue PJ, Beyer EC and Berthoud VM: Autophagy: a pathway that contributes to connexin degradation. J Cell Sci. 124:910–920. 2011. View Article : Google Scholar : PubMed/NCBI
9	Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H and Demetriadou K: A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg. 80:291–300. 1994. View Article : Google Scholar : PubMed/NCBI
10	Milad M, Vidal-Gonzalez I and Quirk G: Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner. Behav Neurosci. 118:389–394. 2004. View Article : Google Scholar : PubMed/NCBI
11	Song SX, Gao JL, Wang KJ, et al: Attenuation of brain edema and spatial learning deficits by the inhibition of NADPH oxidase activity using apocynin following diffuse traumatic brain injury in rats. Mol Med Rep. 7:327–331. 2013.
12	Meijer AJ and Codogno P: Autophagy: regulation and role in disease. Critical Rev Clin Lab Sci. 46:210–240. 2009. View Article : Google Scholar
13	Zhang YB, Li SX, Chen XP, et al: Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neurosci Bull. 24:143–149. 2008. View Article : Google Scholar : PubMed/NCBI
14	Sun LQ, Gao JL, Cui CM, et al: Astrocytic p-connexin 43 regulates neuronal autophagy in the hippocampus following traumatic brain injury in rats. Mol Med Rep. 9:77–82. 2014.
15	Luo CL, Li BX, Li QQ, et al: Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice. Neuroscience. 184:54–63. 2011. View Article : Google Scholar : PubMed/NCBI
16	Rami A, Volkmann T and Winckler J: Effective reduction of neuronal death by inhibiting gap junctional intercellular communication in a rodent model of global transient cerebral ischemia. Exp Neurol. 170:297–304. 2001. View Article : Google Scholar : PubMed/NCBI
17	Ohsumi A, Nawashiro H, Otani N, Ooigawa H, Toyooka T and Shima K: Temporal and spatial profile of phosphorylated connexin43 after traumatic brain injury in rats. J Neurotrauma. 27:1255–1263. 2010. View Article : Google Scholar : PubMed/NCBI
18	Sasaki T and Garant PR: Fate of annular gap junctions in the papillary cells of the enamel organ in the rat incisor. Cell Tissue Res. 246:523–530. 1986. View Article : Google Scholar : PubMed/NCBI
19	Leach DH and Oliphant LW: Degradation of annular gap junctions of the equine hoof wall. Acta Anat (Basel). 120:214–219. 1984. View Article : Google Scholar
20	Zhang YB, Li SX, Chen XP, et al: Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neurosci Bull. 24:143–149. 2008. View Article : Google Scholar : PubMed/NCBI