Aluminum-induced defective mitochondrial metabolism perturbs cytoskeletal dynamics in human astrocytoma cells.
Although aluminum (Al), a known environmental toxin, has been implicated in a variety of neurological disorders, the molecular mechanism responsible for these conditions is not fully understood. In this report, we demonstrate the ability of Al to trigger mitochondrial dysfunction and ineffective adenosine triphosphate (ATP) production. This situation severely affected cytoskeletal dynamics. Whereas the control cells had well-defined structures, the Al-exposed astrocytoma cells appeared as globular structures. Creatine kinase (CK) and profilin-2, two critical modulators of cellular morphology, were markedly diminished in the astrocytoma cells treated with Al. Antioxidants such as alpha-ketoglutarate and N-acetylcysteine mitigated the occurrence of the globular-shaped cells promoted by Al toxicity. Taken together, these data reveal an intricate link between ATP metabolism and astrocytic dysfunction and provide molecular insights into the pathogenesis of Al-induced neurological diseases.
Lemire
J
J
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada.
Mailloux
R
R
Puiseux-Dao
S
S
Appanna
V D
VD
D000111:Acetylcysteine / Q000008:administration & dosage; D000255:Adenosine Triphosphate / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D003402:Creatine Kinase / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D007656:Ketoglutaric Acids / Q000008:administration & dosage; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism
D000975:Antioxidants; D007656:Ketoglutaric Acids; D051304:Profilins; D000255:Adenosine Triphosphate; D000535:Aluminum; D003402:Creatine Kinase; D000111:Acetylcysteine