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The apoptotic effects of oxidative stress and antiapoptotic effects of caspase inhibitors on rat notochordal cells.
Spine (Phila Pa 1976). 2007 Oct 15; 32(22):2443-8.S

Abstract

STUDY DESIGN

Western blotting and flow cytometric analyses were performed using rat notochordal cells.

OBJECTIVE

To demonstrate the apoptotic effect of oxidative stress and the antiapoptotic effects of caspase inhibitors on rat notochordal cells.

SUMMARY OF BACKGROUND DATA

Although oxidative stress causes apoptosis in many cell types, its effect on the apoptosis of notochordal cell and antiapoptotic effects of caspase inhibitors on the oxidative stress-induced apoptosis are unknown.

METHODS

Cultured rat notochordal cells were exposed to oxidative stress [500 micromol/L of hydrogen peroxide (H2O2)]. To determine the oxidative stress-induced apoptotic pathways, activations of caspases (-3, -8, and -9) as well as cleavages of Bid and poly (ADP-ribose) polymerase (PARP) were evaluated with Western blotting 6 hours after oxidative stress. To elucidate the antiapoptotic effects of caspase inhibitors on the oxidative stress induced-apoptosis, apoptotic rates of notochordal cells with or without treatment of specific caspase inhibitors (z-IETD-fmk for caspase-8, z-LEHD-fmk for caspase-9, and z-DEVD-fmk for caspase-3) were quantified by flow cytometry.

RESULTS

Oxidative stress significantly increased apoptosis of rat notochordal cells (2.1% vs. 4.75%, P = 0.008) and led to activations of initiators of intrinsic (caspases-9) and extrinsic (caspase-8) pathways as well as their common executioner (caspase-3). It also caused cleavages of Bid and PARP. Flow cytometric analysis showed that inhibition of only one of the intrinsic and extrinsic pathways by caspase-9 inhibitor (4.75% vs. 3.56%, P = 0.31) and caspase-8 inhibitor (4.75% vs. 5.24%, P = 0.84) did not significantly suppress the oxidative stress-induced apoptosis. However, inhibition of both pathways by caspase-3 inhibitor significantly reduced the oxidative stress-induced apoptosis (4.75% vs. 2.64%, P = 0.008) to the control level (2.1% vs. 2.64%, P = 0.15).

CONCLUSION

Oxidative stress caused apoptosis of rat notochordal cells via both intrinsic and extrinsic (Type I and Type II) pathways. Because caspase inhibitors are being used in clinical trials, inhibition of both pathways using caspase inhibitors might be of future therapeutic importance in oxidative stress-induced apoptosis of notochordal cells. Our results suggest that inhibition of inappropriate or premature oxidative stress-induced apoptosis of notochordal cells may delay the starting point of disc degeneration.

Authors+Show Affiliations

Department of Orthopedic Surgery, St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18090083

Citation

Kim, Ki-Won, et al. "The Apoptotic Effects of Oxidative Stress and Antiapoptotic Effects of Caspase Inhibitors On Rat Notochordal Cells." Spine, vol. 32, no. 22, 2007, pp. 2443-8.
Kim KW, Ha KY, Lee JS, et al. The apoptotic effects of oxidative stress and antiapoptotic effects of caspase inhibitors on rat notochordal cells. Spine (Phila Pa 1976). 2007;32(22):2443-8.
Kim, K. W., Ha, K. Y., Lee, J. S., Rhyu, K. W., An, H. S., & Woo, Y. K. (2007). The apoptotic effects of oxidative stress and antiapoptotic effects of caspase inhibitors on rat notochordal cells. Spine, 32(22), 2443-8.
Kim KW, et al. The Apoptotic Effects of Oxidative Stress and Antiapoptotic Effects of Caspase Inhibitors On Rat Notochordal Cells. Spine (Phila Pa 1976). 2007 Oct 15;32(22):2443-8. PubMed PMID: 18090083.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The apoptotic effects of oxidative stress and antiapoptotic effects of caspase inhibitors on rat notochordal cells. AU - Kim,Ki-Won, AU - Ha,Kee-Yong, AU - Lee,Jun-Seok, AU - Rhyu,Kee-Won, AU - An,Howard S, AU - Woo,Young-Kyun, PY - 2007/12/20/pubmed PY - 2008/1/17/medline PY - 2007/12/20/entrez SP - 2443 EP - 8 JF - Spine JO - Spine (Phila Pa 1976) VL - 32 IS - 22 N2 - STUDY DESIGN: Western blotting and flow cytometric analyses were performed using rat notochordal cells. OBJECTIVE: To demonstrate the apoptotic effect of oxidative stress and the antiapoptotic effects of caspase inhibitors on rat notochordal cells. SUMMARY OF BACKGROUND DATA: Although oxidative stress causes apoptosis in many cell types, its effect on the apoptosis of notochordal cell and antiapoptotic effects of caspase inhibitors on the oxidative stress-induced apoptosis are unknown. METHODS: Cultured rat notochordal cells were exposed to oxidative stress [500 micromol/L of hydrogen peroxide (H2O2)]. To determine the oxidative stress-induced apoptotic pathways, activations of caspases (-3, -8, and -9) as well as cleavages of Bid and poly (ADP-ribose) polymerase (PARP) were evaluated with Western blotting 6 hours after oxidative stress. To elucidate the antiapoptotic effects of caspase inhibitors on the oxidative stress induced-apoptosis, apoptotic rates of notochordal cells with or without treatment of specific caspase inhibitors (z-IETD-fmk for caspase-8, z-LEHD-fmk for caspase-9, and z-DEVD-fmk for caspase-3) were quantified by flow cytometry. RESULTS: Oxidative stress significantly increased apoptosis of rat notochordal cells (2.1% vs. 4.75%, P = 0.008) and led to activations of initiators of intrinsic (caspases-9) and extrinsic (caspase-8) pathways as well as their common executioner (caspase-3). It also caused cleavages of Bid and PARP. Flow cytometric analysis showed that inhibition of only one of the intrinsic and extrinsic pathways by caspase-9 inhibitor (4.75% vs. 3.56%, P = 0.31) and caspase-8 inhibitor (4.75% vs. 5.24%, P = 0.84) did not significantly suppress the oxidative stress-induced apoptosis. However, inhibition of both pathways by caspase-3 inhibitor significantly reduced the oxidative stress-induced apoptosis (4.75% vs. 2.64%, P = 0.008) to the control level (2.1% vs. 2.64%, P = 0.15). CONCLUSION: Oxidative stress caused apoptosis of rat notochordal cells via both intrinsic and extrinsic (Type I and Type II) pathways. Because caspase inhibitors are being used in clinical trials, inhibition of both pathways using caspase inhibitors might be of future therapeutic importance in oxidative stress-induced apoptosis of notochordal cells. Our results suggest that inhibition of inappropriate or premature oxidative stress-induced apoptosis of notochordal cells may delay the starting point of disc degeneration. SN - 1528-1159 UR - https://www.unboundmedicine.com/medline/citation/18090083/The_apoptotic_effects_of_oxidative_stress_and_antiapoptotic_effects_of_caspase_inhibitors_on_rat_notochordal_cells_ L2 - https://doi.org/10.1097/BRS.0b013e318157395a DB - PRIME DP - Unbound Medicine ER -