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Expression of apoptotic protease activating factor-1 (Apaf-1) gradually decreases during brain development, and this decrease is likely responsible for the decreased sensitivity of brain tissue to apoptosis. However, the mechanism by which Apaf-1 expression is decreased remains elusive. In the present study, we found that four microRNAs (miR-23a/b and miR-27a/b) of miR-23a-27a-24 and miR-23b-27b-24 clusters play key roles in modulating the expression of Apaf-1. First, we found that miR-23a/b and miR-27a/b suppressed the expression of Apaf-1 in vitro. Interestingly, the expression of the miR-23-27-24 clusters in the mouse cortex gradually increased in a manner that was inversely correlated with the pattern of Apaf-1 expression. Second, hypoxic injuries during fetal distress caused reduced expression of the miR-23b and miR-27b that was inversely correlated with an elevation of Apaf-1 expression during neuronal apoptosis. Third, we made neuronal-specific transgenic mice and found that overexpressing the miR-23b and miR-27b in mouse neurons inhibited the neuronal apoptosis induced by intrauterine hypoxia. In conclusion, our results demonstrate, in central neural system, that miR-23a/b and miR-27a/b are endogenous inhibitory factors of Apaf-1 expression and regulate the sensitivity of neurons to apoptosis. Our findings may also have implications for the potential target role of microRNAs in the treatment of neuronal apoptosis-related diseases. 相似文献
323.
Lotus japonicus, orderly information on its symbiotic partner Mesorhizobium loti is still lacking. To improve this situation, we review the history of the M. loti nomenclature and compare several strains commonly used, since classification of rhizobia has been confusing during the last
decade. We also refer to the large symbiotic gene cluster, the `symbiosis island', on M. loti chromosome. Then, molecular techniques for M. loti currently available and required to cope with the post-genome sequencing era will be summarized. Finally, we review current
knowledge on the structure of M. loti Nod factors.
Received 29 August 2000/ Accepted in revised form 25 September 2000 相似文献
324.