Beneficial effects of treatment with cystamine on brain in NZB/W F1 mice.
The involvement of the central nervous system (CNS) or neuropsychosis has been reported in patients with systemic lupus erythematosus (SLE) and considered a major cause of long-standing functional impairment and mortality. However, little is known in the improvement of the brain abnormality in SLE. To investigate the effect and mechanism of cystamine on brain in SLE, NZB/W F1 mice were used as the animal model. Gel zymography, caspase-3 activity assay and Western blots were performed to elucidate the effect of cystamine. Significant reduction of matrix metalloproteinases (MMP)-9/MMP-2 ratio and urokinase-type plasminogen activator (uPA) expression was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Significant increase of heat-shock protein (HSP)-70 and HSP27 was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Additionally, significant reduction of mitochondrial dependent apoptosis was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group by increasing BCL-2 and reducing caspase-9, Bad, and Apaf-1 expression. Moreover, increased phosphorylated p65 (NF-kappaB) protein was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group. These experimental results firstly demonstrated the beneficial effects of cystamine on brain in NZB/W F1 mice and suggested the therapeutic potential in patients with neuropsychiatric SLE (NP-SLE).
Hsu
Tsai-Ching
TC
Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan.
Chen
Yi-Chen
YC
Lai
Wen-Xian
WX
Chiang
Szu-Yi
SY
Huang
Chih-Yang
CY
Tzang
Bor-Show
BS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003538:Cystamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020945:Lupus Vasculitis, Central Nervous System / Q000188:drug therapy / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008814:Mice, Inbred NZB; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486699:Hspb2 protein, mouse; D051996:Transcription Factor RelA; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D003538:Cystamine