| Autor: |
Baby, Santhosh M., Roy, Arijit, Mokashi, Anil M., Lahiri, Sukhamay |
| Předmět: |
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| Zdroj: |
Histochemistry & Cell Biology; Nov2003, Vol. 120 Issue 5, p343-352, 10p |
| Abstrakt: |
The present investigation provides for the first time, unambiguous information on the occurrence of hypoxia-inducible factors (HIF-1α and HIF-1β proteins) in normoxia (Nx) and their interaction with hypoxia (Hx) and intracellular Fe2+ chelation in the rat carotid body (CB) glomus cells. HIF-1α bound to HIF-1β translocated into the nucleus is identified on the basis of immunohistochemistry and immunofluorescence. In Nx, a weak expression of HIF-1α was observed in CB glomus cells. However, exposure of CB and glomus cells to Hx (Po2≃7 Torr) and Nx with ciclopirox olamine (CPX, 5 μM) for 1 h showed a significant (P<0.001) increase in HIF-1α protein. The CBs and glomus cells exposed to Nx, Hx, and Nx with CPX showed a constant level of HIF-1β protein expression. HIF-1α subunit is continuously synthesized and degraded under normoxic conditions, while it accumulates rapidly following exposure to low oxygen tensions. Hydroxylation of HIF-1α by prolyl hydroxylase for proteasomal degradation was dependent on iron, 2-oxoglutarate, and oxygen concentration. The intracellular iron that acts as a cofactor for prolyl hydroxylase activity belongs to the labile iron pool and can be easily chelated. Thus, chelation of intracellular labile iron by CPX in Nx significantly increased HIF-1α in CB glomus cells. Thus, the results are consistent with the hypothesis that HIF-1α which is present in the glomus cells translocates to the nucleus during exposure to Hx and to CPX in Nx. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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