PMID- 10903612
OWN - NLM
STAT- MEDLINE
DCOM- 20001004
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 108
IP  - 7
DP  - 2000 Jul
TI  - Microcystic cyanobacteria extract induces cytoskeletal disruption and 
      intracellular glutathione alteration in hepatocytes.
PG  - 605-9
AB  - Microcystins are a group of highly liver-specific toxins, although their exact 
      mechanisms of action remain unclear. We examined the effects of microcystic 
      cyanobacteria extract (MCE) collected from a contaminated water source on the 
      organization of cellular microtubules (MTs) and microfilaments (MFs) in 
      hepatocytes. We also investigated the effects on lactate dehydrogenase (LDH) 
      leakage and intracellular glutathione (GSH). Primary cultured rat hepatocytes 
      exposed to MCE (equivalent to 125 microg/mL lyophilized algae cells) showed a 
      characteristic disruption of MTs and MFs in a time-dependent manner. Under these 
      conditions, MCE caused aggregation of MTs and MFs and a severe loss of MTs in 
      some cells. Moreover, MCE-induced cytoskeletal alterations preceded the LDH 
      leakage. On the other hand, the treatment of cells with MCE led to a 
      dose-dependent increase of intracellular GSH. However, time-course study showed a 
      biphasic change of intracellular GSH levels with a significant increase in the 
      initial stage followed by a decrease after prolonged treatment. Furthermore, 
      pretreatment with N-acetylcystein (NAC), a GSH precursor, significantly enhanced 
      the intracellular GSH level and decreased the MCE-induced cytotoxicity as well as 
      cytoskeleton changes. In contrast, buthionine-(S, R)-sulfoximine, a specific GSH 
      synthesis inhibitor, increased the cell susceptibility to MCE-induced 
      cytotoxicity by depleting the intracellular GSH level. These findings suggest 
      that intracellular GSH plays an important role in MCE-induced cytotoxicity and 
      cytoskeleton changes in primary cultured rat hepatocytes. Increasing 
      intracellular GSH levels protect cells from MCE-induced cytotoxicity and 
      cytoskeleton changes.
FAU - Ding, W X
AU  - Ding WX
AD  - Center for Environmental and Occupational Health, Department of Community, 
      Occupational and Family Medicine, National University of Singapore.
FAU - Shen, H M
AU  - Shen HM
FAU - Ong, C N
AU  - Ong CN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Bacterial Toxins)
RN  - 0 (Microcystins)
RN  - 0 (Peptides, Cyclic)
RN  - 77238-39-2 (microcystin)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Bacterial Toxins/*adverse effects
MH  - Cell Culture Techniques
MH  - Cyanobacteria/*chemistry
MH  - Cytoskeleton/diagnostic imaging/*drug effects
MH  - Glutathione/*metabolism
MH  - Liver/cytology/*drug effects/pathology
MH  - Microcystins
MH  - Peptides, Cyclic/*adverse effects
MH  - Rats
MH  - Ultrasonography
PMC - PMC1638175
EDAT- 2000/07/21 11:00
MHDA- 2000/10/07 11:01
PMCR- 2000/07/01
CRDT- 2000/07/21 11:00
PHST- 2000/07/21 11:00 [pubmed]
PHST- 2000/10/07 11:01 [medline]
PHST- 2000/07/21 11:00 [entrez]
PHST- 2000/07/01 00:00 [pmc-release]
AID - sc271_5_1835 [pii]
AID - 10.1289/ehp.00108605 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2000 Jul;108(7):605-9. doi: 10.1289/ehp.00108605.