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There is growing evidence that galectin-1 (GAL-1) and galectin-3 (GAL-3) are involved in the process of axonal regeneration after injury and the pathogenesis of peripheral neuropathies, but the precise roles of these galectins in the peripheral nervous system (PNS) remain unclear. In this paper, we summarized the distribution and possible functions of GAL-1 and GAL-3 in the PNS at mature stages under normal and pathological conditions. Predominant expression of GAL-1 and GAL-3 in isolectin B4 (IB4)-binding small non-peptidergic sensory neurons in dorsal root ganglia (DRG) accords with the involvement of these molecules in nociceptive and thermoceptive functions and GDNF-induced neurite outgrowth. Up-regulation of GAL-1 mRNA/protein in the neurons and Schwann cells upon peripheral nerve injury suggests its active participation in axonal regeneration; both GAL-1 in the reduced and oxidized forms appear to be key molecules for normal onset of Wallerian degeneration and subsequent neurite outgrowth, but the latter lacks lectin activity and may promote the process by stimulating macrophages rather than directly acting on neurons. GAL-3 deficient mice exhibited the acceleration in the process of Wallerian degeneration, but there is room for argument on its pathological roles in axonal regeneration. Up-regulation of GAL-3 protein in immortalized Schwann cells IFRS1 under diabetic conditions and its cytoprotective functions on the cells suggest that it may act as a factor against the progression of diabetic neuropathy, but further evidence is needed to support this idea. All these findings have shed light on both physiological and pathological roles of GAL-1 and GAL-3 in the PNS, and further evidence will be helpful to develop novel strategies for functional restoration after peripheral nerve injury and therapeutic efficacy against diabetic and other neuropathies. [ABSTRACT FROM AUTHOR]

Spontaneous germline mutations generate genetic diversity in populations of sexually reproductive organisms, and are thus regarded as a driving force of evolution. However, the cause and mechanism remain unclear. 8-oxoguanine (8-oxoG) is a candidate molecule that causes germline mutations, because it makes DNA more prone to mutation and is constantly generated by reactive oxygen species in vivo. We show here that endogenous 8-oxoG caused de novo spontaneous and heritable G to T mutations in mice, which occurred at different stages in the germ cell lineage and were distributed throughout the chromosomes. Using exome analyses covering 40.9 Mb of mouse transcribed regions, we found increased frequencies of G to T mutations at a rate of 2×10-7 mutations/base/generation in offspring of Mth1/Ogg1/Mutyh triple knockout (TOY-KO) mice, which accumulate 8-oxoG in the nuclear DNA of gonadal cells. The roles of MTH1, OGG1, and MUTYH are specific for the prevention of 8-oxoG-induced mutation, and 99% of the mutations observed in TOY-KO mice were G to T transversions caused by 8-oxoG; therefore, we concluded that 8-oxoG is a causative molecule for spontaneous and inheritable mutations of the germ lineage cells. [ABSTRACT FROM AUTHOR]

Alkylation of DNA at the O6-position of guanine is one of the most critical events leading to induction of mutation as well as to cancer. The enzyme O6-methylguanine-DNA methyltransferase repairs this and related lesions in DNA. By means of gene targeting, we established mouse lines deficient in the methyltransferase gene and tissues from these mice contained no methyltransferase activity. Administration of methylnitrosourea to these gene-targeted mice led to early death, and normal mice treated in the same manner showed no untoward effects. In mice given methylnitrosourea treatment, the bone marrow became hypocellular and there was a drastic decrease in the numberof leukocytes and platelets, thereby indicating an impaired reproductive capacity of hematopoietic stem cells. Methyltransferase apparently protected these mice from the pancytopenia caused by the alkylating agent. [ABSTRACT FROM PUBLISHER]