Activation of p38 MAPK and expression of TGF-β1 in rat colon enterocytes after whole body γ-irradiation.
OBJECTIVE
To examine the p38 mitogen-activated protein kinase (p38) phosphorylation and transforming growth factor beta 1 (TGF-β1) expression in rat colon enterocytes after irradiation and their contribution to pathology of intestinal radiation disease.


METHODS
Male Wistar rats were irradiated with whole body γ-radiation of 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 Gy ((60)Co, 1.44 Gy.min(-1)). Samples were taken 4 and 24 h after irradiation, immunohistochemically stained, then p38 phosphorylation and TGF-β1 expression were measured in apical and cryptal enterocytes using computer image analysis. In selected groups, morphometric parameters, mitosis and apoptosis were evaluated.


RESULTS
P38 phosphorylation integrated optical density (IOD)-based levels increased 2.4-fold (p ≤ 0.01) and 3.6 to 22.8-fold (p ≤ 0.001) in apical enterocytes 4 h after 0.5 Gy and 24 h after 3-10 Gy, respectively. TGF-β1 IOD-based expression increased 3.3- to 6.9-fold (p ≤ 0.001) and 1.6- to 4.9-fold (p ≤ 0.001) in apical cells 4 h after 0.5-2, 4, 5 Gy and 24 h after 6-10 Gy, respectively. No changes were observed in crypts.


CONCLUSIONS
We found a chronological and dose-dependent order of p38 activation and TGF-β1 expression in apical enterocytes. Transient up-regulation of p38 and TGF-β1 signalling observed 4 h after low-dose irradiation may participate in molecular mechanisms creating cellular over-expression in apical compartment, while persistent patterns measured 24 h after high-dose irradiation might provide protection of remaining cells in order to maintain tissue integrity.
Center of Advanced Studies, University of Defence, Hradec Králové, Czech Republic. jaroslav.pejchal@seznam.cz
Jaroslav
J
Pejchal
Jakub
J
Novotný
Václav
V
Mařák
Jan
J
Osterreicher
Aleš
A
Tichý
Jiřina
J
Vávrová
Zuzana
Z
Sinkorová
Lenka
L
Zárybnická
Eva
E
Novotná
Jaroslav
J
Chládek
Andrea
A
Babicová
Klára
K
Kubelková
Kamil
K
Kuča
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D016764:Cell Polarity / Q000528:radiation effects; D003106:Colon / Q000166:cytology* / Q000528:radiation effects; D020895:Enterocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000528:radiation effects*; D004789:Enzyme Activation / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D008297:Male; D008938:Mitosis / Q000528:radiation effects; D010766:Phosphorylation / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048051:p38 Mitogen-Activated Protein Kinases