Hypoxia-sensitive

Mirnezami, a. H., et ah, Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p5 3-dependent transcription. Curr Biol, 2003, 13(14), 1234-9. 

While rescue of protein synthesis in hypoxia sensitive mammalian cells does not seem feasible without oxygen, exactly such a rescue system seems available to hypoxia tolerant cells (Land and Hochachka, 1995). One underlying rescue mechanism appears to require the overproduction of key elongation factors such as EFla with sustained hypoxia, the latter is overexpressed and accumulates throughout the stress period. 

HYPOXIA-SENSITIVE FUNCTIONS OF HIF 1 AND SP3 ARE REGULATED POST-TRANSCRIPTIONALLY... 

In overview, the hypoxia-sensitive expression of each of these kinds of proteins (EPO, PGK, and LDH), and of other glycolytic enzymes appears to be two-step or two-cycle systems (figure 3.14) the first cycles involve the constitutive expression of key hypoxia-sensitive transcription factors such as HIF 1 and Sp3, while the second cycles of gene expression are mediated by these transcription factors and regulate the biosynthesis of EPO, PGK, LDH, other glycolytic enzymes, and other hypoxia-sensitive gene products. 

Since the expression of other proteins, such as elongation factors, may be similarily regulated, it is tempting to consider that the induction and accumulation (calibrated relative to other proteins) of EF la in hypoxic plant tissue and the hypoxia-sensitive proteins in turtle and rat hepatocytes are under similar two-cycle gene regulation (figure 3.15), although at this time... 

For further control of cancer cell selectivity, Zhu and coworkers developed tumor-hypoxia activated phototrigger systems using coumarin as the photosensitizer and nitro-imidazole as the hypoxia-sensitive imit [143]. Hypoxia-induced nitroimidazole reduction was required before photocleavage of coumarin and etoposide release for anticancer therapy. They showed cancer cell killing in vitro in aerobic conditions after illumination but not in a normal atmosphere. In aerobic tissues, nitroimidazole acts as an electron acceptor, preventing photocleavage and imspedfic drug release in normal tissues. 

K. Kiyose, K. Hanaoka, D. Oushiki, T. Nakamura, M. Kajimura, M. Suematsu, H. Nishimatsu, T. Yamane, T. Terai, Y. Hirata, and T. Nagano, Hypoxia-sensitive fluorescent probes for in vivo real-time fluorescence imaging of acute ischemia, / Am Chem Soc, 132 (45), 15846-8,2010. 

Perhaps surprisingly, given their importance in the developing infant, the carotid chemoreceptors have minimal sensitivity to hypoxia at birth and become more sensitive over the first few days or weeks of life (10-16). Increasing hypoxia sensitivity of the arterial chemoreceptors after birth is termed resetting, and it occurs in both carotid and aortic chemoreceptors (17). Carotid chemoreceptor resetting appears to be modulated by the 4-fold rise in arterial O2 tension that occurs at birth (18-22), raising the possibility that peri- and postnatal hypoxia may impair carotid chemoreceptor development. In addition, perinatal hyperoxia causes... 

An obvious possibility to explain carotid chemoreceptor maturation is that the sensitivity of the O2 sensor itself increases with age. This question cannot be addressed at this time because the identity of the type 1 cell O2 sensor remains unknown, even for the mature carotid body. As discussed above, available evidence suggests that type I cell membrane potential is regulated, in large part, by several K" " currents, some of which are inhibited by hypoxia (89,92,97,98) (Fig. 1). Whether the K" " channels themselves are O2 sensitive or linked to a separate O2 sensor is unknown. Maturational changes in O2 sensitivity of hypoxia-sensitive K" " eurrents could occur by shifts in K" " channel subiuiits, developmental shifts in expression of K" " channel subtypes with different O2 sensitivity, and a variety of other meeh-anisms. However, these possibilities have not been explored. 

Figure 2 Characterization of TASKl in rat cerebellar granule neurons, (a) Subtracted currents evoked by ramp hyperpolarizations from a resting potential of —20 mV to —100 mV on the time scale on the X-axis showing the acid- and hypoxia-sensitive components as indicated. Also shown is the negligible component that is h poxia-sensitive under acidic conditions, (b) Exemplar time course of acid and hypoxia sensitivity of currents measured at —20 mV (c) Current clamp recording of the effect of hypoxia on membrane potential. All recordings were made employing the perforated patch technique.

Youngson C, Nurse, Yeger H, Cutz E. Characterization of membrane currents in pulmonary neuroepithelial bodies hypoxia-sensitive airway chemoreceptors. In O Regan RG, Nolan P, McQueen DS, Paterson DJ, eds. Arterial Chemoreceptors. Cell to System. New York and London Plenum Press, 1994 179-182. 

Lauweryns JM, Cokelaere M. Hypoxia sensitive neuroepithelial bodies, intrapuhnon-ary secretory neuroreceptors undulated by the CNS. Z Zellforsch 1973 145 521-540. 

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