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

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.

A self-destructive nanosweeper that captures and clears amyloid β-peptides

“…Next, the GFP-LC3 transfected N2a cells were incubated with M 3 -Cy5&Aβ 42 (20 μg·mL −1 /20 μM) for 4 h, followed by CLSM observation. Generally, LC3-II was recruited to the autophagosome membrane and thereby formed a green dot of GFP-LC3 when autophagy was activated 36 , 37 . As expected, the CLSM images revealed that most of the M 3 -Cy5 (red signal) colocalized with autophagosomes (GFP-LC3, green signal) (Fig.…”

Role of autophagy in the regulation of epithelial cell junctions

“…57 Following traumatic brain injury (TBI), autophagy inhibition caused increased levels of phosphorylated connexin 43 (pCx43) in hippocampal astrocytes, indicating autophagy based degradation of GJs. 58 A single or several AGJs can be engulfed simultaneously within an individual autophagosome. 54 Furthermore, plasma-membrane bound connexin proteins have been shown to be involved in early biogenesis of autophagosome.…”

Effect of poly‑arginine R18 on neurocyte cell growth via autophagy in traumatic brain injury

“…Autophagy is involved in the pathological and physiological process of numerous diseases. However, no consensus has been reached on the effect of autophagy on organ function (16). A previous study has indicated that autophagy may lead to autophagic cell death or apoptosis, thus aggravating organ dysfunction (17).…”