星狀膠質細胞為中樞神經系統中含量最多的膠質細胞，在中樞神經系統中扮演重要角色；除了能夠調節中樞神經系統為環境中離子及神經傳導物質的恆定，星狀膠質細胞亦能將血管中的養分傳送給神經細胞，供給其代謝所需的能量。六價鉻是一種工業上運用十分廣泛的重金屬，但是被發現對人體具有強烈毒性及致癌性。在本實驗中發現，鉻對於星狀膠質細胞的傷害會隨著處理的濃度與時間增加而增加。以50 μM及100 μM的六價鉻處理星狀膠質細胞24小時之後，發現星狀膠質細胞的觸角有萎縮的現象，並且發現有凋亡小體的構造出現；藉由對細胞核的染色也發現有細胞核濃縮的現象。這些觀察顯示六價鉻可能導致星狀膠質細胞走向細胞凋亡。本實驗中發現鉻會顯著的增加星狀膠質細胞中活化態凋亡蛋白酵素-3（caspases-3）表現量，然而處理capspase-3的專一性抑制劑Z-DEVD-FMK卻無法抑止鉻處理所造成之星狀膠質細胞死亡。以凝膠電泳遷移率變動分析（EMSA）發現活化蛋白-1(AP-1)與DNA的結合能力在鉻處理12小時後有明顯增加，然而以JNK(c-jun N-terminal kinase)抑制劑處理卻無法保護星狀膠質細胞免於鉻所造成之細胞死亡現象。此結果顯示活化蛋白-1的活化並不參與鉻所導致的星狀膠質細胞死亡。我們更進一步發現鉻不會影響星狀膠質細胞中鈣離子濃度的變化，但在鉻處理12小時候發現活性氧物質(ROS)生成量增加；活性氧物質生成量的增加可能是鉻處理六小時候所引發的粒腺體細胞膜電位下降而生成的細胞壓力所導致。此外，藉由鉻處理後發現凋亡引誘蛋白(apoptosis-inducing factor)與核酸內切脢(Endo G)轉位至細胞核的現象，此轉位現象進一步會導致DNA片段化。綜合上述，我們推測鉻所導致的粒腺體功能失常以及活性氧物質的生成引發凋亡引誘蛋白及核酸內切脢釋放，進一步造成星狀膠質細胞死亡。

Astrocytes, the most abundant glial cell population in the CNS, play physiological and pathological roles in neuronal activities. In addition to the regulation of ion/neurotransmmitter homeostasis in CNS microenvironment, astrocytes also transport glucose from capillaries to supply the energy fuel for neuronal metabolism. Chromium (VI) is widely used in many industries, but has serious toxic and carcinogenic effects on human. In this study, we found that chromium (VI) was toxic to astrocytes along with the dose and time-dependent pattern. Morphological examination also indicated that treatment with 50 and 100 μM of chromium (VI) for 24 h caused astrocytic process withdrawal and the apoptotic-body feature. Nuclear staining also showed nuclei condensation. These observations indicate that chromium (VI) could induce astrocytic apoptosis. Although chromium (VI) significantly increased cleaved caspase-3 levels in astrocytes, the selective inhibitor of activated caspase-3 failed to suppress chromium (VI)-induced astrocytic cell death. Electrophoresis motility shift assay (EMSA) showed AP-1 DNA binding activity was increased at 12 h after chromium (VI) treatment, while JNK (c-Jun N-terminal kinase) inhibitor did not protect astrocytes from chromium (VI)-treated insult. These results indicated that AP-1 activation did not involve chromium (VI)-induced astrocytic cell death. We further found that chromium (VI) did not affect intracellular calcium levels in astrocytes, but it induced an increase in ROS levels at 12 h. This increase could be resulted from cellular stress induced by the reduction of mitochondrial membrane potential at 6 h after chromium (VI) treatment. Furthermore, AIF and Endo G translocation into the nucleus was observed in chromium (VI)-treated astrocytes, leading to DNA fragmentation. Taken together, we conclude that chromium (VI)-induced mitochondrial dysfunction and ROS signaling trigger AIF and Endo G release which in turn contribute to chromium (VI)-induced astrocytic apoptosis.

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