title: The effects of swainsonine on the activity and expression of α-mannosidase in BRL-3A cells.
abstract: Swainsonine (SW) is the principal toxic ingredient of locoweeds, which can cause intensive vacuolar degeneration because of α-mannosidase inhibition after animal ingestion. While SW can lead to obvious liver damage in vivo, the mechanism of hepatotoxic damage caused by SW is not clear. Therefore, BRL-3A cells were treated for 24, 48, and 72 h with SW at various concentrations (0, 700, 900, 1100 μg/mL). The α-mannosidase (AMAN) activity was determined in BRL-3A cells using an enzyme substrate technique. The expression of mRNA and proteins of GM II (MAN2A1) and LAM (MAN2B1) in BRL-3A cells was detected by qPCR and Western-blot. The results showed that SW could significantly reduce the activity of AMAN in a time-dose effect relationship. Compared with the control group, the activity of AMAN significantly decreased only in the group treated with 1100 μg/mL SW for 24 h (P < 0.01), but the activity decreased significantly (P < 0.05 or P < 0.01) in all experimental groups treated for 48 or 72 h. SW also significantly reduced the expression of MAN2A1 and MAN2B1 mRNA and proteins in a time-dose effect relationship (P < 0.05 or P < 0.01), while the inhibition of SW was stronger for MAN2B1 than for MAN2A1. These results suggest that SW can significantly reduce the activity and expression of α-mannosidase thus causing SW-induced hepatotoxic damage.
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors: Hao
authors: H
authors: Lu
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors: Feng
authors: F
authors: Ma
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors: Huan
authors: H
authors: Wang
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors: Peng-Shuai
authors: PS
authors: Geng
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors: Shan-Shan
authors: SS
authors: Wang
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors: Jian-Guo
authors: JG
authors: Wang
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors: Chen-Chen
authors: CC
authors: Wu
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address: zhby668@126.com.
authors: Bao-Yu
authors: BY
authors: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002681:China; D004794:Enzyme Repression / Q000187:drug effects*; D006056:Golgi Apparatus / Q000187:drug effects / Q000201:enzymology; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D033021:Oxytropis / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017026:Swainsonine / Q000633:toxicity*; D014118:Toxins, Biological / Q000633:toxicity*; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D014118:Toxins, Biological; C000606294:MAN2A1 protein, rat; C000606295:MAN2B1 protein, rat; D043323:alpha-Mannosidase; D017026:Swainsonine
keywords: BRL-3A cells; Locoweed; MAN2A1; MAN2B1; Swainsonine