TY - JOUR
T1 - The crucial role of vitamin C and its transporter (SVCT2) in bone marrow stromal cell autophagy and apoptosis
AU - Sangani, Rajnikumar
AU - Periyasamy-Thandavan, Sudharsan
AU - Pathania, Rajneesh
AU - Ahmad, Saif
AU - Kutiyanawalla, Ammar
AU - Kolhe, Ravindra
AU - Bhattacharyya, Maryka H.
AU - Chutkan, Norman
AU - Hunter, Monte
AU - Hill, William D.
AU - Hamrick, Mark
AU - Isales, Carlos
AU - Fulzele, Sadanand
N1 - Publisher Copyright:
© 2015.
PY - 2015
Y1 - 2015
N2 - Vitamin C is an antioxidant that plays a vital role in various biological processes including bone formation. Previously, we reported that vitamin C is transported into bone marrow stromal cells (BMSCs) through the sodium dependent Vitamin C Transporter 2 (SVCT2) and this transporter plays an important role in osteogenic differentiation. Furthermore, this transporter is regulated by oxidative stress. To date, however, the exact role of vitamin C and its transporter (SVCT2) in ROS regulated autophagy and apoptosis in BMSCs is poorly understood. In the present study, we observed that oxidative stress decreased survival of BMSCs in a dose-dependent manner and induced growth arrest in the G1 phase of the cell cycle. These effects were accompanied by the induction of autophagy, confirmed by P62 and LC3B protein level and punctate GFP-LC3B distribution. The supplementation of vitamin C significantly rescued the BMSCs from oxidative stress by regulating autophagy. Knockdown of the SVCT2 transporter in BMSCs synergistically decreased cell survival even under low oxidative stress conditions. Also, supplementing vitamin C failed to rescue cells from stress. Our results reveal that the SVCT2 transporter plays a vital role in the mechanism of BMSC survival under stress conditions. Altogether, this study has given new insight into the role of the SVCT2 transporter in oxidative stress related autophagy and apoptosis in BMSCs.
AB - Vitamin C is an antioxidant that plays a vital role in various biological processes including bone formation. Previously, we reported that vitamin C is transported into bone marrow stromal cells (BMSCs) through the sodium dependent Vitamin C Transporter 2 (SVCT2) and this transporter plays an important role in osteogenic differentiation. Furthermore, this transporter is regulated by oxidative stress. To date, however, the exact role of vitamin C and its transporter (SVCT2) in ROS regulated autophagy and apoptosis in BMSCs is poorly understood. In the present study, we observed that oxidative stress decreased survival of BMSCs in a dose-dependent manner and induced growth arrest in the G1 phase of the cell cycle. These effects were accompanied by the induction of autophagy, confirmed by P62 and LC3B protein level and punctate GFP-LC3B distribution. The supplementation of vitamin C significantly rescued the BMSCs from oxidative stress by regulating autophagy. Knockdown of the SVCT2 transporter in BMSCs synergistically decreased cell survival even under low oxidative stress conditions. Also, supplementing vitamin C failed to rescue cells from stress. Our results reveal that the SVCT2 transporter plays a vital role in the mechanism of BMSC survival under stress conditions. Altogether, this study has given new insight into the role of the SVCT2 transporter in oxidative stress related autophagy and apoptosis in BMSCs.
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U2 - 10.1016/j.scr.2015.06.002
DO - 10.1016/j.scr.2015.06.002
M3 - Article
C2 - 26210298
AN - SCOPUS:84937793141
SN - 1873-5061
VL - 15
SP - 312
EP - 321
JO - Stem Cell Research
JF - Stem Cell Research
IS - 2
ER -