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  • Proceedings of the National Academy of Sciences  (5)
  • Plum, Lori A.  (5)
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  • Proceedings of the National Academy of Sciences  (5)
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  • 1
    Online Resource
    Online Resource
    UV light suppression of EAE (a mouse model of multiple sclerosis) is independent of vitamin D and its receptor
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 45 ( 2019-11-05), p. 22552-22555
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 45 ( 2019-11-05), p. 22552-22555
    Abstract: Vitamin D and sunlight have each been reported to protect against the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). To date, the contribution of each has been unclear as ultra violet (UV) exposure also causes the generation of vitamin D in the skin. To examine whether the UV based suppression of EAE results, at least, in part from the production of vitamin D, we studied the effect of UV light on EAE in mice unable to produce 7-dehydroxycholesterol (7-DHC), the required precursor of vitamin D. Furthermore, we examined UV suppression of EAE in mice devoid of the vitamin D receptor (VDR). Our results demonstrate that UV light suppression of EAE occurs in the absence of vitamin D production and in the absence of VDR. Future investigations will focus on identifying the pathway responsible for the protective action of UV in EAE and presumably human MS.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1913294116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Salate derivatives found in sunscreens block experimental autoimmune encephalomyelitis in mice
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 32 ( 2017-08-08), p. 8528-8531
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 32 ( 2017-08-08), p. 8528-8531
    Abstract: UV light suppresses experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, in mice and may be responsible for the decreased incidence of MS in equatorial regions. To test this concept further, we applied commercially available sunblock preparations to mice before exposing them to UV radiation. Surprisingly, some of the sunblock preparations blocked EAE without UV radiation. Furthermore, various sunblock preparations had variable ability to suppress EAE. By examining the components of the most effective agents, we identified homosalate and octisalate as the components responsible for suppressing EAE. Thus, salates may be useful in stopping the progression of MS, and may provide new insight into mechanisms of controlling autoimmune disease.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1703995114
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Biologically active noncalcemic analogs of 1α,25-dihydroxyvitamin D with an abbreviated side chain containing no hydroxyl
    Proceedings of the National Academy of Sciences ; 2004
    In:  Proceedings of the National Academy of Sciences Vol. 101, No. 18 ( 2004-05-04), p. 6900-6904
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 18 ( 2004-05-04), p. 6900-6904
    Abstract: Since the discovery of the active metabolite of vitamin D, i.e., 1α,25-dihydroxyvitamin D 3 , there has been a continuous effort to synthesize analogs able to carry out many of the functions of the native hormone without raising serum calcium concentration. The present report provides a series of previously undescribed analogs wherein this goal is realized. We have prepared 2-methylene-19-nor-1α-hydroxyvitamin D analogs of 1,25-(OH) 2 D 3 that possess only two to four carbons of the side chain without a hydroxyl thereon. Compared to 1,25-(OH) 2 D 3 , these analogs are slightly less active in binding to the vitamin D receptor, in causing HL-60 differentiation, and are slightly less active in in vitro transcription assays using the 24-hydroxylase promoter attached to a luciferase reporter gene. Of considerable importance is that these analogs, given to rats at daily doses of up to 70 μg/kg of body weight per day, are either unable or only slightly able to raise serum calcium concentration but are nevertheless able to suppress parathyroid hormone levels in plasma up to 100% and induce 24-hydroxylase mRNA in skin. Because of their ability to act in vivo without raising serum calcium levels, they may be of considerable interest for the systemic treatment of diseases such as psoriasis, cancer, and secondary hyperparathyroidism of renal failure, where a rise in serum calcium is undesirable.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0401656101
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2004
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 4
    Online Resource
    Online Resource
    A potent analog of 1α,25-dihydroxyvitamin D 3 selectively induces bone formation
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 21 ( 2002-10-15), p. 13487-13491
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 21 ( 2002-10-15), p. 13487-13491
    Abstract: 1,25-Dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] is a principal regulator of calcium and phosphorus homeostasis through actions on intestine, kidney, and bone. 1,25(OH) 2 D 3 is not considered to play a significant role in bone formation, except for its role in supporting mineralization. We report here on the properties of 2-methylene-19-nor - (20S)-1α,25(OH) 2 D 3 (2MD), a highly potent analog of 1,25(OH) 2 D 3 that induces bone formation both in vitro and in vivo . Selectivity for bone was first demonstrated through the observation that 2MD is at least 30-fold more effective than 1,25(OH) 2 D 3 in stimulating osteoblast-mediated bone calcium mobilization while being only slightly more potent in supporting intestinal calcium transport. 2MD is also highly potent in promoting osteoblast-mediated osteoclast formation in vitro , a process essential to both bone resorption and formation. Most significantly, 2MD at concentrations as low as 10 −12 M causes primary cultures of osteoblasts to produce bone in vitro . This effect is not found with 1,25(OH) 2 D 3 even at 10 −8 M, suggesting that 2MD might be osteogenic in vivo . Indeed, 2MD (7 pmol/day) causes a substantial increase (9%) in total body bone mass in ovariectomized rats over a 23-week period. 1,25(OH) 2 D 3 (500 pmol three times a week) only prevented the bone loss associated with ovariectomy and did not increase bone mass. These results indicate that 2MD is a potent bone-selective analog of 1,25(OH) 2 D 3 potentially effective in treating bone loss diseases.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.202471299
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 5
    Online Resource
    Online Resource
    Vitamin D binding protein is required to utilize skin-generated vitamin D
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 49 ( 2019-12-03), p. 24527-24532
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 49 ( 2019-12-03), p. 24527-24532
    Abstract: Vitamin D is produced in the skin following exposure to sunlight. Ultraviolet (UV) B (UVB, 280–310 nm) results in isomerization of 7-dehydrocholesterol to previtamin D that spontaneously isomerizes to vitamin D. This pool of skin-derived vitamin D is the major source of vitamin D for animals. However, the mechanisms by which it becomes available remain undefined. It has been assumed that cutaneous vitamin D is transported into the circulation by vitamin D binding protein (DBP), but experimental evidence is lacking. To determine whether cutaneous vitamin D is transported by DBP, we utilized DBP −/− mice that were made vitamin D-deficient. These animals lack measurable 25(OH)D in blood and are hypocalcemic. As controls, DBP +/+ animals were vitamin D depleted and made equally hypocalcemic. UV irradiation of DBP +/+ animals restored serum calcium and serum 25(OH)D while the same treatment of DBP −/− animals failed to show either a serum calcium or 25(OH)D response despite having normal vitamin D production in skin. Intravenous injection of small amounts of recombinant DBP to the vitamin D-deficient DBP −/− mice restored the response to UV light. These results demonstrate a requirement for DBP to utilize cutaneously produced vitamin D.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1915442116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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