Epigallocatechin-3-gallate modulates germ cell apoptosis through the SAFE/Nrf2 signaling pathway
Affiliations
Affiliations
- Department of Biochemistry, Faculty of Medicine, Kuwait University, 24923, Safat, 13110, Jabriyah, Kuwait. malmaghrebi@hsc.edu.kw.
- Department of Biochemistry, Faculty of Medicine, Kuwait University, 24923, Safat, 13110, Jabriyah, Kuwait.
Abstract
To examine the role of the transcription factor nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) and the SAFE pathway (JAK/STAT) in the induction of germ cell apoptosis (GCA) and the protective role of epigallocatechin-3-gallate (EGCG) during testicular ischemia reperfusion injury (tIRI). Male Sprague-Dawley rats (n = 18) were divided into three groups: sham, unilateral tIRI, tIRI + epigallocatechin-3-gallate (EGCG, 50 mg/Kg). Unilateral tIRI was induced by 1-h ischemia followed by 4-h reperfusion, and EGCG was injected i.p. 30-min post ischemia. Immuno-histological analyses were used to detect spermatogenesis, oxidative DNA damage, and the immuno-expression of the JAK2, STAT3, and STAT1. Biochemical assays were used to investigate the oxidative, apoptosis proteins and enzymes, while Western blot was used to detect the expression of NOX and Nrf2. Expression of apoptosis-related genes was measured by real-time PCR. During tIRI, there was a clear damage to spermatogenesis associated with decreased activities of SOD, CAT, and GPx and increased levels of lipid peroxidation and oxidative DNA damage. In addition, GCA was indicated by the activation of caspase1, PARP, decreased gene expression of survivin and increased Bax to Bcl2 ratio. In contrast to lowered Nrf2 levels, NOX levels were augmented and phosphorylation of JAK2, STAT3, and STAT1 was increased. Pre-perfusion treatment with EGCG prevented the above modulations. The coordinated activation of the SAFE pathway and suppression of Nrf2 contribute to the tIRI-induced oxidative damages and GCA, which were modulated by EGCG.
Keywords: EGCG; Germ cell apoptosis; Ischemia reperfusion injury; Nrf2; SAFE; Survivin.
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KMEL References
References
-
- Pharmacol Rep. 2016 Feb;68(1):101-8 - PubMed
-
- Urology. 2016 Aug;94:312.e1-8 - PubMed
-
- J Biol Chem. 2012 Mar 23;287(13):9873-86 - PubMed
-
- Biochem Biophys Res Commun. 2012 Apr 6;420(2):434-9 - PubMed
-
- Antioxid Redox Signal. 2018 Dec 10;29(17):1727-1745 - PubMed
-
- Age (Omaha). 1997 Jul;20(3):127-40 - PubMed
-
- Basic Res Cardiol. 2018 Jan 15;113(2):9 - PubMed
-
- Biochem Biophys Res Commun. 2010 May 7;395(3):342-7 - PubMed
-
- Tohoku J Exp Med. 2012;228(3):259-66 - PubMed
-
- Int J Urol. 2005 Jan;12(1):81-9 - PubMed
-
- Oxid Med Cell Longev. 2013;2013:737591 - PubMed
-
- BJU Int. 2005 Jul;96(1):175-80 - PubMed
-
- Int J Prev Med. 2013 Jun;4(6):624-30 - PubMed
-
- Oxid Med Cell Longev. 2017;2017:3172692 - PubMed
-
- Free Radic Biol Med. 2018 Feb 20;116:159-171 - PubMed
-
- Mol Cell Endocrinol. 2016 Feb 15;422:203-210 - PubMed
-
- Int J Mol Sci. 2017 Dec 20;18(12): - PubMed
-
- Oxid Med Cell Longev. 2008 Oct-Dec;1(1):15-24 - PubMed
-
- Nucleic Acids Res. 2010 Sep;38(17):5718-34 - PubMed
-
- Oxid Med Cell Longev. 2012;2012:929285 - PubMed
-
- Pharmacol Res. 2011 Aug;64(2):105-12 - PubMed
-
- Reprod Biomed Online. 2015 Oct;31(4):544-56 - PubMed
-
- J Mol Med (Berl). 2012 Nov;90(11):1333-42 - PubMed
-
- Food Chem Toxicol. 2008 Apr;46(4):1271-8 - PubMed
-
- Folia Med (Plovdiv). 2006;48(3-4):16-21 - PubMed
-
- Free Radic Biol Med. 2010 Nov 15;49(9):1368-79 - PubMed