活性氧被認(rèn)為是導(dǎo)致癌癥和衰老的元兇,,還被視為男性不育的原因之一。但日本研究人員在動(dòng)物實(shí)驗(yàn)中發(fā)現(xiàn),,如果體內(nèi)活性氧不足,,同樣會(huì)導(dǎo)致不育。這是由于活性氧不足會(huì)導(dǎo)致精原干細(xì)胞難以增殖,。
活性氧是氧氣的同素異形體,,其非常容易與其他物質(zhì)發(fā)生反應(yīng),是一種強(qiáng)氧化劑,?;钚匝蹙哂袣⑺啦≡任⑸锏墓δ埽矔?huì)對細(xì)胞內(nèi)的蛋白質(zhì)等產(chǎn)生不良影響,,引發(fā)阿爾茨海默氏癥等疾病,。
日本京都大學(xué)等機(jī)構(gòu)的研究人員培養(yǎng)出實(shí)驗(yàn)鼠的精原干細(xì)胞,然后向干細(xì)胞添加抑制活性氧功能的藥物,,結(jié)果精原干細(xì)胞變得難以增殖,。而如果向精原干細(xì)胞添加與實(shí)驗(yàn)鼠正常細(xì)胞相同濃度的活性氧,則精原干細(xì)胞的增殖得到促進(jìn),。
研究小組指出,,過剩的活性氧曾被認(rèn)為會(huì)降低精子功能,導(dǎo)致不育,,但是本項(xiàng)實(shí)驗(yàn)顯示,,活性氧不足也會(huì)引發(fā)男性不育。這個(gè)發(fā)現(xiàn)提供了治療不育的新思路,。
相關(guān)論文已刊登在新一期《細(xì)胞—干細(xì)胞》雜志上,。(生物谷Bioon.com)
Cell Stem Cell DOI:10.1016/j.stem.2013.04.001
ROS Are Required for Mouse Spermatogonial Stem Cell Self-Renewal
Hiroko Morimoto, Kazumi Iwata, Narumi Ogonuki, Kimiko Inoue, Ogura Atsuo, Mito Kanatsu-Shinohara, Takeshi Morimoto, Chihiro Yabe-Nishimura, Takashi Shinohara
Reactive oxygen species (ROS) generation is implicated in stem cell self-renewal in several tissues but is thought to be detrimental for spermatogenesis as well as spermatogonial stem cells (SSCs). Using cultured SSCs, we show that ROS are generated via the AKT and MEK signaling pathways under conditions where the growth factors glial cell line-derived neurotrophic factor and fibroblast growth factor 2 drive SSC self-renewal and, instead, stimulate self-renewal at physiological levels. SSCs depleted of ROS stopped proliferating, but they showed enhanced self-renewal when ROS levels were increased by the addition of hydrogen peroxide, which induced the phosphorylation of stress kinases p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK). Moreover, ROS depletion in vivo decreased SSC number in the testis, and NADPH oxidase 1 (Nox1)-deficient SSCs exhibited reduced self-renewal division upon serial transplantation. These results suggest that ROS generated by Nox1 play critical roles in SSC self-renewal via the activation of the p38 MAPK and JNK pathways.