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N-acetyl-L-cysteine counteracts oxidative stress and prevents H2O2 induced germ cell apoptosis through down-regulation of caspase-9 and JNK/c-Jun.
Mol Reprod Dev. 2011 Feb; 78(2):69-79.MR

Abstract

The mechanism of H(2)O(2) induced oxidative stress leading to male germ cell apoptosis was earlier reported from our laboratory. In the present study, we investigated the mechanisms by which N-acetyl-L-cysteine (NAC, which is highly cell specific with strong antioxidant and anti-genotoxic properties), stimulated cell survival under such conditions. Co-incubation with 5 mM NAC significantly (P<0.001) reduced the germ cell apoptosis induced by 10 µM H(2)O(2). Lipid peroxidation was brought down with significant restoration of activities of antioxidant enzymes, SOD, GST, and catalase. Expression of pro-apoptotic marker, Bax up-regulated following H(2)O(2) exposure, was reversed back to control levels. In contrast, expression of anti-apoptotic Bcl-2 and phospho-Akt revealed a completely opposite trend. While caspase-8 activity remained unaffected, NAC successfully attenuated the increased activities of caspase-3 and -9 in the H(2) O(2) treated cells. Simultaneously, the increased expression of caspase-9, phospho-JNK, and phospho-c-Jun after H(2)O(2) treatment was down-regulated by NAC. The above findings indicate that the mechanism of inhibition of H(2)O(2) induced male germ cell apoptosis by NAC is mediated through regulation of caspase-9 and JNK.

Authors+Show Affiliations

Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, New Delhi, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21254278

Citation

Maheshwari, Ankur, et al. "N-acetyl-L-cysteine Counteracts Oxidative Stress and Prevents H2O2 Induced Germ Cell Apoptosis Through Down-regulation of Caspase-9 and JNK/c-Jun." Molecular Reproduction and Development, vol. 78, no. 2, 2011, pp. 69-79.
Maheshwari A, Misro MM, Aggarwal A, et al. N-acetyl-L-cysteine counteracts oxidative stress and prevents H2O2 induced germ cell apoptosis through down-regulation of caspase-9 and JNK/c-Jun. Mol Reprod Dev. 2011;78(2):69-79.
Maheshwari, A., Misro, M. M., Aggarwal, A., Sharma, R. K., & Nandan, D. (2011). N-acetyl-L-cysteine counteracts oxidative stress and prevents H2O2 induced germ cell apoptosis through down-regulation of caspase-9 and JNK/c-Jun. Molecular Reproduction and Development, 78(2), 69-79. https://doi.org/10.1002/mrd.21268
Maheshwari A, et al. N-acetyl-L-cysteine Counteracts Oxidative Stress and Prevents H2O2 Induced Germ Cell Apoptosis Through Down-regulation of Caspase-9 and JNK/c-Jun. Mol Reprod Dev. 2011;78(2):69-79. PubMed PMID: 21254278.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-acetyl-L-cysteine counteracts oxidative stress and prevents H2O2 induced germ cell apoptosis through down-regulation of caspase-9 and JNK/c-Jun. AU - Maheshwari,Ankur, AU - Misro,Man M, AU - Aggarwal,Archana, AU - Sharma,Rajnesh K, AU - Nandan,Deoki, Y1 - 2011/01/20/ PY - 2010/10/06/received PY - 2010/12/06/accepted PY - 2011/1/22/entrez PY - 2011/1/22/pubmed PY - 2011/8/23/medline SP - 69 EP - 79 JF - Molecular reproduction and development JO - Mol Reprod Dev VL - 78 IS - 2 N2 - The mechanism of H(2)O(2) induced oxidative stress leading to male germ cell apoptosis was earlier reported from our laboratory. In the present study, we investigated the mechanisms by which N-acetyl-L-cysteine (NAC, which is highly cell specific with strong antioxidant and anti-genotoxic properties), stimulated cell survival under such conditions. Co-incubation with 5 mM NAC significantly (P<0.001) reduced the germ cell apoptosis induced by 10 µM H(2)O(2). Lipid peroxidation was brought down with significant restoration of activities of antioxidant enzymes, SOD, GST, and catalase. Expression of pro-apoptotic marker, Bax up-regulated following H(2)O(2) exposure, was reversed back to control levels. In contrast, expression of anti-apoptotic Bcl-2 and phospho-Akt revealed a completely opposite trend. While caspase-8 activity remained unaffected, NAC successfully attenuated the increased activities of caspase-3 and -9 in the H(2) O(2) treated cells. Simultaneously, the increased expression of caspase-9, phospho-JNK, and phospho-c-Jun after H(2)O(2) treatment was down-regulated by NAC. The above findings indicate that the mechanism of inhibition of H(2)O(2) induced male germ cell apoptosis by NAC is mediated through regulation of caspase-9 and JNK. SN - 1098-2795 UR - https://www.unboundmedicine.com/medline/citation/21254278/N_acetyl_L_cysteine_counteracts_oxidative_stress_and_prevents_H2O2_induced_germ_cell_apoptosis_through_down_regulation_of_caspase_9_and_JNK/c_Jun_ L2 - https://doi.org/10.1002/mrd.21268 DB - PRIME DP - Unbound Medicine ER -