Altered expression of the vitamin D metabolizing enzymes CYP27B1 and CYP24A1 under the context of prostate aging and pathologies

Campolina-Silva, Gabriel Henrique; Barata, Maria C.; Werneck-Gomes, Hipácia; Maria, Bruna T.; Mahecha, Germán Arturo Bohórquez; Belleannée, Clémence; Oliveira, Cleida A.

doi:10.1016/j.jsbmb.2021.105832

Cited by 6 publications

(3 citation statements)

References 56 publications

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“…Actually it is known that VitD system is altered by aging since the muscular VDR 58 has been reported to be less expressed while the renal 24‐hydroxylase (CYP24A1) which turns all form of VitD in an inactivate form, calcitroic acid, has been reported to be more expressed 59 . Some authors reported that in the prostate, the 1α‐hydroxylase (CYP27B1) protein expression decrease and CYP24A1 protein expression increase during aging 60 . Nevertheless, such results are not retrieved yet in muscle where both enzymes seems to be unchanged during aging 61 …”

Section: Discussionmentioning

confidence: 99%

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Vitamin D deficiency contributes to overtraining syndrome in excessive trained C57BL/6 mice

Talvas,

Norgieux,

Burban

et al. 2023

Scandinavian Med Sci Sports

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Overtraining syndrome is a condition resulting from excessive training load associated with inadequate recovery and poor sleep quality, leading to performance decrements and fatigue. Here we hypothesized that vitamin D (VitD) deficiency is a lead factor in the development of the overtraining syndrome. To test this hypothesis, two groups of 60‐week‐old C57BL/6 mice followed a 16‐week excessive eccentric‐based overtraining by excessive downhill running with or without dietary VitD depletion (EX and EX‐D− groups). Two control groups were trained by uphill running at the same load with or without VitD depletion (CX and CX‐D− groups). Handgrip strength decreased throughout the protocol for all groups but the decrease was sharper in EX‐D− group (VitD × training, p = 0.0427). At the end of the protocol, the mass of Triceps brachii muscle, which is heavily stressed by eccentric contractions, was reduced in eccentric‐trained groups (training effect, p = 0.0107). This atrophy was associated with a lower concentration of the anabolic myokine IL‐15 (training effect, p = 0.0314) and a tendency to a higher expression of the atrogene cathepsin‐L (training effect, p = 0.0628). VitD depletion led to a 50% decrease of the fractional protein synthesis rate in this muscle (VitD effect, p = 0.0004) as well as decreased FGF21 (VitD effect, p = 0.0351) and increased osteocrin (VitD effect, p = 0.038) concentrations that would lead to metabolic defects. Moreover, the proportion of anti‐inflammatory Th2 lymphocytes was significantly decreased by the combination of eccentric training with VitD depletion (vitD × training, p = 0.0249) suggesting a systemic inflammation. Finally, exploratory behavior time of mice was decreased by VitD depletion (VitD effect, p = 0.0146) suggesting a cognitive dysfunction. Our results suggest that VitD deficiency exacerbates the effects of overtraining.

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Section: Discussionmentioning

confidence: 99%

“…59 Some authors reported that in the prostate, the 1α-hydroxylase (CYP27B1) protein expression decrease and CYP24A1 protein expression increase during aging. 60 Nevertheless, such results are not retrieved yet in muscle where both enzymes seems to be unchanged during aging. drivers of overtraining syndrome.…”

Section: Genesmentioning

confidence: 97%

Vitamin D deficiency contributes to overtraining syndrome in excessive trained C57BL/6 mice

Talvas,

Norgieux,

Burban

et al. 2023

Scandinavian Med Sci Sports

View full text Add to dashboard Cite

show abstract

“…In prostate cancer, expression of these enzymes as well as VDR and LPR2 is shown to be both increased and decreased compared to normal prostate (Figure 2). In human non-pathological prostate samples, CYP27B1 men (>60 years), whereas an inverse expression pattern was observed for the CYP gene [41]. This decline in the expression of vitamin D-metabolizing enzymes corresp to an age-related decline in intraprostatic calcitriol levels, indicating that age-depen loss of the potential protective effects of calcitriol is a potential confounder in clinical ies.…”

Section: Vitamin D Metabolism Vitamin D Status and Biological Actions...mentioning

confidence: 93%

Discordant Health Implications and Molecular Mechanisms of Vitamin D in Clinical and Preclinical Studies of Prostate Cancer: A Critical Appraisal of the Literature Data

Fendler,

Stephan,

Ralla

et al. 2024

IJMS

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Clinical and preclinical studies have provided conflicting data on the postulated beneficial effects of vitamin D in patients with prostate cancer. In this opinion piece, we discuss reasons for discrepancies between preclinical and clinical vitamin D studies. Different criteria have been used as evidence for the key roles of vitamin D. Clinical studies report integrative cancer outcome criteria such as incidence and mortality in relation to vitamin D status over time. In contrast, preclinical vitamin D studies report molecular and cellular changes resulting from treatment with the biologically active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol) in tissues. However, these reported changes in preclinical in vitro studies are often the result of treatment with biologically irrelevant high calcitriol concentrations. In typical experiments, the used calcitriol concentrations exceed the calcitriol concentrations in normal and malignant prostate tissue by 100 to 1000 times. This raises reasonable concerns regarding the postulated biological effects and mechanisms of these preclinical vitamin D approaches in relation to clinical relevance. This is not restricted to prostate cancer, as detailed data regarding the tissue-specific concentrations of vitamin D metabolites are currently lacking. The application of unnaturally high concentrations of calcitriol in preclinical studies appears to be a major reason why the results of preclinical in vitro studies hardly match up with outcomes of vitamin D-related clinical studies. Regarding future studies addressing these concerns, we suggest establishing reference ranges of tissue-specific vitamin D metabolites within various cancer entities, carrying out model studies on human cancer cells and patient-derived organoids with biologically relevant calcitriol concentrations, and lastly improving the design of vitamin D clinical trials where results from preclinical studies guide the protocols and endpoints within these trials.

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Vitamin D, inflammation, and cancer

Kallay,

Schepelmann,

Buburuzan

2024

Feldman and Pike's Vitamin D

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Altered expression of the vitamin D metabolizing enzymes CYP27B1 and CYP24A1 under the context of prostate aging and pathologies

Cited by 6 publications

References 56 publications

Vitamin D deficiency contributes to overtraining syndrome in excessive trained C57BL/6 mice

Vitamin D deficiency contributes to overtraining syndrome in excessive trained C57BL/6 mice

Discordant Health Implications and Molecular Mechanisms of Vitamin D in Clinical and Preclinical Studies of Prostate Cancer: A Critical Appraisal of the Literature Data

Vitamin D, inflammation, and cancer

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