Enhanced p62 expression triggers concomitant autophagy and apoptosis in a rat chronic spinal cord compression model.
Chronic spinal cord compression is the result of mechanical pressure on the spinal cord, which in contrast to traumatic spinal cord injury, leads to slowly progressing nerve degeneration. These two types of spinal cord injuries may trigger similar mechanisms, including motoric nerve cell apoptosis and autophagy, however, depending on differences in the underlying injury severity, nerve reactions may predominantly involve the conservation of function or the initiation of functions for the removal of irreversibly damaged cells. p62 is a multidomain adapter protein, which is involved in apoptosis and cell survival as well as autophagy, and is a common component of protein aggregations in neurodegenerative diseases. In the present study, a rat chronic spinal cord compression model was used, in which the spinal cord was progressively compressed for six weeks and then constantly compressed for another 10 weeks. As a result Basso, Beattie and Bresnahan locomotor scaling revealed a gradual score decrease until the 6th week followed by constant recovery until the 16th week after spinal cord compression was initiated. During the first eight weeks of the experiment, p62 and nuclear factor-κB (NF-κB) were increasingly expressed up to a constant plateau at 12-16 weeks, whereas caspase 3 exhibited a marginally enhanced expression at 8 weeks, however, reached a constant maximum peak 12-16 weeks after the beginning of spinal cord compression. It was hypothesized that, in the initial phase of spinal cord compression, enhanced p62 expression triggered NF-κB activity, directing the cell responses mainly to cell survival and autophagy, whereas following eight weeks of spinal cord compression, caspase 3 was additionally activated indicating cumulative elimination of irreversibly damaged nerve cells with highly activated autophagy.
Department of Orthopaedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China.
Zhi
Z
Chen
Department of Emergency and Trauma, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
Qingge
Q
Fu
Department of Orthopaedics, Shanghai Jiading Central Hospital, Shanghai 201800, P.R. China.
Baoliang
B
Shen
Department of Orthopaedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China.
Xuan
X
Huang
Department of Orthopaedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China.
Kun
K
Wang
Department of Orthopaedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China.
Ping
P
He
Department of Orthopaedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China.
Fengning
F
Li
Department of Orthopaedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China.
Fan
F
Zhang
Department of Orthopaedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China.
Hongxing
H
Shen
D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D000071456:Sequestosome-1 Protein; D013117:Spinal Cord Compression / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D006360:Heat-Shock Proteins; D016328:NF-kappa B; D000071456:Sequestosome-1 Protein; C491079:Sqstm1 protein, rat; D053148:Caspase 3