Investigation of AGE, their receptor and NF-kappaB activation and apoptosis in patients with ATTR and Gelsolin amyloidosis.
Transthyretin (TTR) and gelsolin amyloidoses represent two types of hereditary amyloidosis in which point mutations in the respective protein lead to conformational changes of the protein with subsequent amyloid fibril formation.



Tissues from Finnish gelsolin amyloid patients, Danish, Japanese and Swedish ATTR patients were immunostained for AGE, RAGE, NF-kappaB, PARP, and caspases 3 and 8.



Amyloid was heavily deposited in myocard, kidney and gastrointestinal tract of all patients. Immunoreactive areas to AGE and RAGE were detected in the heart, kidney, rectum, gut and appendix. AGE and RAGE were well co-localised with amyloid deposits. In five out of 14 patients neither NF-kappaB activation nor induction of apoptosis marked by positive immunostaining for NF-kappaB, PARP, or caspases 3 and 8 was found, and markers of apoptosis were detected in some samples without accompanying NF-kappaB activation.



Our results suggest that both AGE and RAGE may have a common role in evolution of TTR and gelsolin-related amyloidoses. Apart from AGE-RAGE interactions both amyloid proteins may directly bind to RAGE and result in cellular perturbations; but in view of this study cytotoxic effects other than those triggered by activation of NF-kappaB or apoptosis should be considered.
Anan
Intissar
I
Department of Medicine, Umea University Hospital, Sweden. intissar.anan@medicin.umu.se
Kiuru-Enari
Sari
S
Obayashi
Konen
K
Ranløv
Poul Jørgen
PJ
Ando
Yukio
Y
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D001065:Appendix / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D003224:Congo Red / Q000737:chemistry; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D018260:Gelsolin / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D011228:Prealbumin / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D012007:Rectum / Q000378:metabolism / Q000473:pathology
D000682:Amyloid; D015415:Biomarkers; D018260:Gelsolin; D017127:Glycation End Products, Advanced; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D011228:Prealbumin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D003224:Congo Red