Mitochondrial modulation of apoptosis induced by low-dose radiation in mouse testicular cells / 生物医学与环境科学（英文）

ABSTRACT

<p><b>OBJECTIVE</b>To investigate whether apoptosis induced by low-dose radiation (LDR) is regulated by mitochondrial pathways in testicular cells.</p><p><b>METHODS</b>Male mice were exposed to whole-body LDR, and changes in mitochondrial function and in expression of apoptotic factors were analyzed in the testicular cells as follows. Total nitric-oxide synthase (T-NOS) and Na+/K+ ATPase activities were biochemically assayed. Reactive oxygen species (ROS) and mitochondrial membrane potential (&Delta;ψm) were determined by flow cytometry using fluorescent probes. Levels of mRNAs encoding cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) were quantified by real-time reverse-transcription PCR (RT-PCR). Expression of Cyt c, AIF, caspase-9, and caspase-3 at the protein level was assessed by western blotting and immunohistochemistry.</p><p><b>RESULTS</b>LDR induced an increase in T-NOS activity and ROS levels, and a decrease in Na+/K+ ATPase activity and mitochondrial &Delta;ψm, in the testicular cells. The intensity of these effects increased with time after irradiation and with dose. The cells showed remarkable swelling and vacuolization of mitochondria, and displayed a time- and dose-dependent increase in the expression of Cyt c, AIF, procaspase-9, and procaspase-3. Activation of the two procaspases was confirmed by detection of the cleaved caspases. The changes in expression of the four apoptotic factors were mostly limited to spermatogonia and spermatocytes.</p><p><b>CONCLUSION</b>LDR can induce testicular cell apoptosis through mitochondrial signaling pathways.</p>