Involvement of p53 and Bcl-2 family proteins in regulating programmed cell death and proliferation in human embryogenesis.
Homeostasis and development in vertebrates are regulated by cell proliferation, differentiation and death. Permeability of mitochondrial membranes, a decisive feature of apoptosis, is regulated by Bcl-2 family regulators. Protein p53 is able to reduce bcl-2 and promote bax expression. This study focused on the immunohistochemical detection of the expression levels of Bcl-2 family regulators (anti-apoptotic Bcl-2 and Bcl-XL, pro-apoptotic Bcl-Xs and Bax), p53, and PCNA as a marker of proliferation, together with the evaluation of the level of apoptosis in human embryos (anlage of limbs, axial skeleton, metanephros, and intestine). Expression of observed proteins was assessed by a three-step immunohistochemistry and evidenced by the double-staining technique. Apoptosis was detected by the TUNEL technique. This study provided circumstantial evidence of the exclusive role of Bcl-2 and Bcl-XL proteins in the inhibition of apoptosis - only rarely were the Bcl-2/ Bcl-XL positive cells stained by TUNEL. The role of pro-apoptotic members of Bcl-2 family remains ambiguous, as TUNEL positive cells are both Bax/Bcl-Xs positive and negative. This study provided substantial evidence that expression patterns of observed proteins are neither fully explainable by "rheostat" theory, nor are the findings obtained from animal model tissue or cell culture commonly applicable to human embryos.
Prochazkova
J
J
Department of Histology and Embryology, Medical Faculty of Palacky University Hnevotinska 3, 775 15 Olomouc, Czech Republic.
Lichnovsky
V
V
Kylarova
D
D
Erdosova
B
B
Vranka
P
P
D017209:Apoptosis / Q000502:physiology*; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism*; D047108:Embryonic Development / Q000502:physiology*; D005121:Extremities / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D009928:Organ Specificity; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014018:Tissue Distribution; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53