Pathways involved in testicular germ cell apoptosis induced by H2O2in vitro

Maheshwari, Ankur; Misro, M. M.; Aggarwal, Archana; Sharma, R. K.; Nandan, Devki

doi:10.1111/j.1742-4658.2008.06831.x

Cited by 92 publications

(82 citation statements)

References 46 publications

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“…Our findings are similar to several reports from other groups with respect to the mechanisms of apoptosis in testicular germ cells induced by ischemia, irradiation, and excitotoxicity. For example, Maheshwari et al (2009) demonstrated that H 2 O 2 -elicited apoptosis of testicular germ cells is associated with activation of the p53, Bax, Fas/Fasl, and a simultaneous decrease in the Bcl-2 expression. It was also observed by Chaki et al (2006) that an elevated expression of cell death effector Bax may contribute to the rat germ cell apoptosis with estradiol-3-benzoate administered.…”

Section: Discussionmentioning

confidence: 99%

Involment of p53, Bax, and Bcl‐2 pathway in microcystins‐induced apoptosis in rat testis

Xie

et al. 2011

Environmental Toxicology

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It has been reported that microcystins (MCs) could accumulate in the gonads of mammals and MCs exposure exerts obvious toxic effects on male reproductive system of mammals. We have comfirmed that MCs could accumulate and induce apoptosis in rat testis. The p53, Bax, and Bcl-2 protein play important roles in mitochondria-dependent apoptotic pathway, and this study aimed to investigate whether the p53, Bax, and Bcl-2 pathway is involved in microcystins-induced apoptosis in rat testis and discussed the possible mechanisms. Our results show that MCs led to persistent increase of transcriptional and protein level of P53 and Bax expression but led to decrease of Bcl-2 expression, resulting in an increased ratio of Bax to Bcl-2, which might contribute to apoptotic cell death of rat testis following MCs treatment. The increased ratio of expression of Bax to that of Bcl-2 induced by MCs suggests their important role in MCs-induced apoptosis in rat testis tissue.

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Section: Discussionmentioning

confidence: 99%

Involment of p53, Bax, and Bcl‐2 pathway in microcystins‐induced apoptosis in rat testis

Xie

et al. 2011

Environmental Toxicology

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“…It has been proposed that the Bcl-2 family proteins are either germ cell survival or death modulators [Knudson et al 1995;Mahmoud et al 2009;Yan et al 2000]. Functions of the Bcl-2 related proteins comprise pro-apoptotic (Bax, Bad, and Bid) and anti-apoptotic (Bcl-2, Bcl-xL) proteins [Knudson et al 1995;Maheshwari et al 2009;Yamamoto et al 2000]. Induction of Bax acute stress may promote changes in mitochondrial membrane permeability and release cytochrome C into the cytosol [Blatt and Glick 2001].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it is known that the testes extrinsic apoptotic pathway involves the activation of the Fas receptor and its ligand (FasL), expressed by Sertoli, spermatocyte, and Leyding cells. Once bound to its ligand, Fas can trigger the apoptotic event [Pentikainen et al 1999;Porcelli et al 2006], by a caspase-8 dependent mechanism [Maheshwari et al 2009;Said et al 2004]. Caspase-8 is required for caspase-3 cleavage [Said et al 2004] that is necessary to trigger apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Intrinsic and extrinsic apoptotic pathways are involved in rat testis by cold water immersion-induced acute and chronic stress

Juárez-Rojas

García-Lorenzana²,

Martínez

et al. 2015

Systems Biology in Reproductive Medicine

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Testicular apoptosis is activated by stress, but it is not clear which signaling pathway is activated in response to stress. The aim of this study was to investigate whether intrinsic, extrinsic, or both apoptotic signaling pathways are activated by acute and chronic stress. Adult male rats were subjected to cold water immersion-induced stress for 1, 20, 40, and 50 consecutive days. The seminiferous tubules:apoptotic cell ratio was assayed on acute (1 day) and chronic (20, 40, 50 days) stress. Apoptotic markers, including cleaved-caspase 3 and 8, the pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were also determined after acute and chronic stress induction. Additionally, epididymal sperm quality was evaluated, as well as corticosterone and testosterone levels. An increase in tubule apoptotic cell count percentage after an hour of acute stress and during chronic stress induction was observed. The apoptotic cells rate per tubule increment was only detected one hour after acute stress, but not with chronic stress. Accordingly, there was an increase in Bax, cleaved caspase-8 and caspase-3 proapoptotic proteins with a decrease of anti-apoptotic Bcl-2 in both acutely and chronically stressed male testes. In addition, sperm count, viability, as well as total and progressive motility were low in chronically stressed males. Finally, the levels of corticosterone increased whereas testosterone levels decreased in chronically stressed males. Activation of the extrinsic apoptotic pathway was shown by cleaved caspase-8 increase whereas the intrinsic apoptotic pathway activation was determined by the increase of Bax, along with Bcl-2 decrease, making evident a cross-talk between these two pathways with the activation of caspase-3. These results suggest that both acute and chronic stress can potentially activate the intrinsic/extrinsic apoptosis pathways in testes. Chronic stress also reduces the quality of epididymal spermatozoa, possibly due to a decrease in testosterone.

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“…For heat stress, cells were incubated at 43 8C for 20 min (Saitoh & Hinchey 2000). Experiments with low doses of H 2 O 2 were performed for 1 h (Maheshwari et al 2009). …”

Section: Stress and Drug Treatmentmentioning

confidence: 99%

SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells

Shrivastava¹,

Pekar²,

Grosser³

et al. 2010

Reproduction

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Small ubiquitin-like modifiers (SUMO) proteins have been implicated in cellular stress response in different tissues, but whether sumoylation has a similar role during spermatogenesis is currently unknown. In this study, changes in the levels of both free SUMO isoforms and high-molecular weight (HMW) SUMO conjugates were monitored before and after the induction of different types of cellular stresses. Using cell lines and primary cells freshly isolated from mouse testes, significant changes were detected in the levels of SUMO1 and SUMO2/3 conjugates following short exposure of the cells to heat stress and oxidative stress. While high concentrations of H 2 O 2 caused an increase in protein sumoylation, low concentrations of H 2 O 2 mostly caused protein desumoylation. Immunofluorescence studies localized SUMO to the sites of DNA double-strand breaks in stressed germ cells and during meiotic recombination. To study the effect of oxidative stress in vivo, animals exposed to tobacco smoke for 12 weeks were used. Changes in sumoylation of HMW proteins were consistent with their oxidative damage in the tobacco-exposed mice. Our results are consistent with the important roles of different SUMO isoforms in stress responses in germ cells. Furthermore, this study identified topoisomerase 2 a as one of the targets of sumoylation during normal spermatogenesis and under stress.

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Pathways involved in testicular germ cell apoptosis induced by H₂O₂in vitro

Cited by 92 publications

References 46 publications

Involment of p53, Bax, and Bcl‐2 pathway in microcystins‐induced apoptosis in rat testis

Involment of p53, Bax, and Bcl‐2 pathway in microcystins‐induced apoptosis in rat testis

Intrinsic and extrinsic apoptotic pathways are involved in rat testis by cold water immersion-induced acute and chronic stress

SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells

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