Testosterone Regulation of Homocysteine Metabolism Modulates Redox Status in Human Prostate Cancer Cells

Prudova, Anna; Albin, Matthias M.; Bauman, Zachary M.; Lin, Alexander; Vitvitsky, Victor; Banerjee, Ruma

doi:10.1089/ars.2007.1712

Cited by 35 publications

(35 citation statements)

References 43 publications

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“…tGSH levels of birds hatched from T-injected eggs were also similar to those found in great tit nestlings treated with a high dose of this GSH inhibitor (Galván and Alonso-Alvarez, 2008). These findings could support the idea that the larger breast stripe size detected in T-treated birds could have been due to oxidative stress promoted by this hormone (Alonso-Alvarez et al, 2007), which would decrease GSH levels (Prudova et al, 2007). However, the difference in tGSH levels between birds hatched from T-injected and control eggs was clearly nonsignificant, and it must be mentioned that the expression of phenotypic traits can vary between years in the same population.…”

Section: Discussionsupporting

confidence: 74%

“…mobilization of alternative antioxidants) (Galván and AlonsoAlvarez, 2008). Furthermore, T might increase susceptibility to oxidative stress in birds (Alonso-Alvarez et al, 2007) and might decrease GSH levels in humans (Prudova et al, 2007). Therefore, if yolk T increases the expression of the black breast stripe, we predict that this should be associated with a decrease in GSH levels and a compensatory increase in plasma antioxidants.…”

Section: Introductionmentioning

confidence: 95%

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Yolk testosterone shapes the expression of a melanin-based signal in great tits: an antioxidant-mediated mechanism?

Galván

Alonso‐Álvarez

2010

Journal of Experimental Biology

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SUMMARYConspicuous traits produced by melanin deposition in integuments are often involved in visual communication. The information content of melanin-based signals is unclear as their expression is tightly controlled by genes and, apparently, is less dependent on individual condition. In birds, high heritabilities have been attributed to melanin-based plumages, often on the basis of eggswapping manipulations (cross-fostering experiments). However, it is well known that female birds can differentially transfer testosterone to the egg yolk. Furthermore, high testosterone levels have been related to high oxidative stress. As we recently found that oxidative stress experienced during development influences the expression of melanin-based traits, here we manipulated the level of yolk testosterone in great tits (Parus major) to assess the influence of this maternal effect on the expression of the black breast stripe, a well-known melanin-based signal. We predicted that fledglings hatched from eggs with high testosterone levels will not only show larger black stripes but also experience changes in their antioxidant machinery. Indeed, the size of the black stripe of great tits hatched from testosterone-injected eggs was almost double that of controls. Furthermore, the same individuals showed a trend to higher levels of circulating antioxidants, which suggests an adaptive response against some testosterone-induced oxidative challenge.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 95%

Yolk testosterone shapes the expression of a melanin-based signal in great tits: an antioxidant-mediated mechanism?

Galván

Alonso‐Álvarez

2010

Journal of Experimental Biology

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“…Androgens, including testosterone, are known to regulate the redox system. In particular, treatment of androgen-responsive PCA cells with testosterone is reported to decrease antioxidant response and enhance cell susceptibility to oxidative stress (44). Moreover, decreased HO-1 protein levels were found in ventral prostate from castrated rats compared with controls, whereas administration of androgen increased HO-1 expression (45).…”

Section: Discussionmentioning

confidence: 99%

A Novel Experimental Heme Oxygenase-1–Targeted Therapy for Hormone-Refractory Prostate Cancer

Alaoui‐Jamali

Bismar

Gupta³

et al. 2009

Cancer Research

112

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Heme oxygenase-1 (HO-1), a member of the heat shock protein family, plays a key role as a sensor and regulator of oxidative stress. Herein, we identify HO-1 as a biomarker and potential therapeutic target for advanced prostate cancer (PCA). Immunohistochemical analysis of prostate tissue using a progression tissue microarray from patients with localized PCA and across several stages of disease progression revealed a significant elevation of HO-1 expression in cancer epithelial cells, but not in surrounding stromal cells, from hormonerefractory PCA (HRPCA) compared with hormone-responsive PCA and benign tissue. Silencing the ho-1 gene in HRPCA cells decreased the HO-1 activity, oxidative stress, and activation of the mitogen-activated protein kinase-extracellular signalregulated kinase/p38 kinase. This coincided with reduced cell proliferation, cell survival, and cell invasion in vitro, as well as inhibition of prostate tumor growth and lymph node and lung metastases in vivo. The effect of ho-1 silencing on these oncogenic features was mimicked by exposure of cells to a novel selective small-molecule HO-1 inhibitor referred to as OB-24. OB-24 selectively inhibited HO-1 activity in PCA cells, which correlated with a reduction of protein carbonylation and reactive oxygen species formation. Moreover, OB-24 significantly inhibited cell proliferation in vitro and tumor growth and lymph node/lung metastases in vivo. A potent synergistic activity was observed when OB-24 was combined with Taxol. Together, these results establish HO-1 as a potential therapeutic target for advanced PCA. [Cancer Res 2009;69(20):8017-24]

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“…It was previously revealed that testosterone exposure significantly down-regulated the enzyme, cystathionine beta-synthase (CBS), which catalyzes the committing step in the transsulfuration pathway, and resulted in significant decreases in intracellular glutathione and sulfate levels (Prudova et al 2007). Furthermore, in the androgen synthesis pathway, the androgen metabolite of dehydroepiandrosterone (DHEA) is important to biochemically regulating the production of testosterone.…”

Section: Why Males Might Be More Vulnerablementioning

confidence: 99%

Developmental neurotoxicants and the vulnerable male brain: a systematic review of suspected neurotoxicants that disproportionally affect males

Kern¹,

Homme

King³

et al. 2017

Acta Neurobiologiae Experimentalis

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The prevalence of neurodevelopmental disorders (NDs), including autism spectrum disorder, attention-deficit/hyperactivity disorder, tic disorder, obsessive-compulsive disorder, and emotional disturbances, has increased notably in the past few decades.To date, debate continues as to the origins of NDs. Increases in widespread exposure to and bioaccumulation of chemical neurotoxicants have paralleled the upsurge in NDs, and are suggested to be causal agents for NDs. One consistent aspect of NDs is the male preponderance. This review considers the issue of male preponderance by reviewing the gender-specific neurotoxic effects of recognized neurotoxicant chemicals to assess their possible etiology in NDs. This investigation consisted of a systematic literature review of original studies published from 1970-2016 on suspected neurotoxicants, to examine whether they have a disproportionate adverse effect based on gender. Based on that review, the neurotoxicants exhibiting consistent gender-specific effects, with exposed males being more affected (than similarly exposed females), were: lead, Thimerosal/ethylmercury, some organochlorine pesticides (e.g., dieldrin, endosulfan, and heptachlor), and air pollution. The next group identified were neurotoxicants exhibiting gender-specific neurotoxic effects, with males being somewhat (but not consistently) more affected than females: mercury vapor, polychlorinated biphenyls (PCBs), and organophosphate pesticides. Finally, there was a group of studies in which the neurotoxicants exhibited apparent gender-related neurotoxic effects but failed to show whether exposed males were consistently more affected than females: inorganic mercury salts, methylmercury species, and certain endocrine disruptors (e.g., phthalates and BPA). The overall conclusion from the studies reviewed was that the brain in males is more vulnerable to many toxic exposures than it is in females. Evidence suggests that the reasons for the male brain being more vulnerable include:(1) greater glutathione availability in females; (2) greater sulfate-based detoxification capacity in females; (3) potentiating effects of co-exposure to neurotoxicants and testosterone; (4) greater neuroinflammatory response in males; (5) reduced vulnerability to oxidative stress in females; and (6) neuroprotective effects of female hormones (estrogen and progesterone), especially in the reduction of inflammation and oxidative stress.

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Testosterone Regulation of Homocysteine Metabolism Modulates Redox Status in Human Prostate Cancer Cells

Cited by 35 publications

References 43 publications

Yolk testosterone shapes the expression of a melanin-based signal in great tits: an antioxidant-mediated mechanism?

Yolk testosterone shapes the expression of a melanin-based signal in great tits: an antioxidant-mediated mechanism?

A Novel Experimental Heme Oxygenase-1–Targeted Therapy for Hormone-Refractory Prostate Cancer

Developmental neurotoxicants and the vulnerable male brain: a systematic review of suspected neurotoxicants that disproportionally affect males

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