Apoptosis and its pathway in early post-implantation embryos of diabetic rats.
It has been reported that diabetes-induced inappropriate apoptosis in embryos during neurulation may be one of the mechanisms leading to neural tube defects. We studied apoptosis and the apoptotic pathway occurring in early post-implantation period embryos of non-diabetic and streptozotocin (STZ)-induced diabetic rats. In quantitative RT-PCR, bax mRNA was constantly expressed to similar degree in embryos of non-diabetic and diabetic rats, while the expression of bcl-2 mRNA was significantly decreased in diabetic rat embryos compared to non-diabetic rat embryos. The increased number of terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-positive cells occurred selectively in the primitive brains of diabetic rat embryos compared to non-diabetic rat embryos. Immunohistochemical studies revealed that, in mirror sections, the staining of Bax and activated caspase-3 were observed in the TUNEL-positive cell area, but the expression of Bcl-2 in these apoptotic cells was generally too low to be detected. These results suggest that a Bax-regulated mitochondrial cytochrome c-mediated caspase-3 activation pathway might be involved in the diabetic embryopathy.
Sun
Fuyan
F
Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan.
Kawasaki
Eiji
E
Akazawa
Shoichi
S
Hishikawa
Yositaka
Y
Sugahara
Kazuyuki
K
Kamihira
Shimeru
S
Koji
Takehiko
T
Eguchi
Katsumi
K
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D045304:Cytochromes c / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004622:Embryo, Mammalian / Q000737:chemistry / Q000166:cytology*; D047108:Embryonic Development; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases