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Pathogen research abs 1 || Pathogen research abs 2 || Pathogen research abs 3 || Pathogen research abs 4 || Pathogen research abs 5 || Hormone and endocrine research abs 1 || Hormone and endocrine research abs 2 || Hormone and endocrine research abs 3 || Hormone and endocrine research abs 4 || Hormone and endocrine research abs 5







J Endocrinol. 2002 Jun;173(3):525-32.
Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes.

Ravid A, Rubinstein E, Gamady A, Rotem C, Liberman UA, Koren R.

Basil and Gerald Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Beilinson Campus, Petah Tikva 49100, Israel. araviost.tau.ac.il

In addition to its known effects on keratinocyte proliferation and differentiation, the hormonal form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to protect keratinocytes from UV- and chemotherapy-induced damage. Epidermal keratinocytes contain both the machinery needed to produce 1,25(OH)(2)D(3) and vitamin D receptors. The activation of the stress-activated protein kinases (SAPKs), such as c-Jun N-terminal kinase (JNK) and p38, is an early cellular response to stress signals and an important determinant of cell fate. This study examines whether modulation of these SAPKs is associated with the effects of 1,25(OH)(2)D(3) on keratinocytes under stress. HaCaT keratinocytes were exposed to heat shock, hyperosmotic concentrations of sorbitol, the epidermal growth factor receptor tyrosine kinase inhibitor AG1487, the pro-inflammatory cytokine tumor necrosis factor alpha, and H(2)O(2). These stresses activated both SAPKs. Pretreatment with 1,25(OH)(2)D(3) inhibited the activation of JNK by all stresses and the activation of p38 by heat shock, AG1478 and tumor necrosis factor alpha. Under the same conditions, treatment with 1,25(OH)(2)D(3) protected HaCaT keratinocytes from cytotoxicity induced by exposure to H(2)O(2) and hyperosmotic shock. The effect of 1,25(OH)(2)D(3) was dose-dependent, already apparent at nanomolar concentrations, and time-dependent, maximal after a 24-h pre-incubation. We suggest that inhibition of SAPK activation may account for some of the well-documented protective effects of 1,25(OH)(2)D(3) on epidermal cells during exposure to UV or chemotherapy and may also be related to the anti-inflammatory actions of the hormone in skin.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12065242&dopt=Abstract



EMBO J. 2002 Jun 17;21(12):3029-38.
Homeodomain protein ATHB6 is a target of the protein phosphatase ABI1 and regulates hormone responses in Arabidopsis.

Himmelbach A, Hoffmann T, Leube M, Hohener B, Grill E.

Lehrstuhl fur Botanik, Technische Universitat Munchen, Am Hochanger 4, D-85350 Freising, Germany.

ABI1, a protein phosphatase 2C, is a key component of signal transduction in ARABIDOPSIS: It regulates diverse responses to the phytohormone abscisic acid (ABA) such as stomatal closure, seed dormancy and inhibition of vegetative growth. By analysing proteins capable of interacting with ABI1, we have identified the homeodomain protein ATHB6 as a regulator of the ABA signal pathway. Critical for interaction between ATHB6 and ABI1 is an intact protein phosphatase domain and the N-terminal domain of ATHB6 containing the DNA-binding site. ATHB6 recognizes a cis-element present in its promoter, which encompasses the core motif (CAATTATTA) that mediated ATHB6- and ABA-dependent gene expression in protoplasts. In addition, transgenic plants containing a luciferase gene controlled by the ATHB6 promoter documented a strong ABA-inducible expression of the reporter which was abrogated in the ABA-insensitive abi1 mutant. Arabidopsis plants with constitutive expression of the transcriptional regulator revealed ABA insensitivity in a subset of ABI1-dependent responses. Thus, the homeodomain protein ATHB6 seems to represent a negative regulator of the ABA signal pathway and to act downstream of ABI1.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12065416&dopt=Abstract



J Androl. 2002 Jul-Aug;23(4):491-7.
Cell-cell interactions in the testis of adjuvant-induced arthritic rat.

Asirvatham AL, Bruot BC.

Department of Biological Sciences, Kent State University, Kent, Ohio, USA.

Rats with adjuvant-induced arthritis (AA) have low levels of serum testosterone, and production of testosterone reportedly is influenced by macrophage secretory products. This study was undertaken to understand the mechanism mediating this hypoandrogenism. Testicular macrophages from AA and nonarthritic (NA)rats were cultured, and conditioned media was added to testicular interstitial cells and Percoll-purified cells from NA rats. Testosterone production by interstitial cells stimulated with luteinizing hormone (LH) and incubated with adjuvant-induced arthritic macrophage conditioned medium (AAMCM) was significantly lower than in cells incubated with nonarthritic macrophage conditioned medium (NAMCM). However, there was no difference in testosterone production by Percoll-purified Leydig cells and those stimulated with LH when incubated with AAMCM or NAMCM. To determine whether an intermediary cell type was involved in mediating inhibition of testosterone production, AAMCM and NAMCM were added to a reconstituted preparation of testicular interstitial cells. Addition of AAMCM restored the inhibitory effect, suggesting that arthritic hypoandrogenism is mediated by cell-cell interaction. These results suggest that a factor produced by macrophages from AA rats appears to mediate testosterone production by acting in conjunction with other cells in the testicular interstitium.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12065455&dopt=Abstract



Biol Psychiatry. 2002 Dec 15;52(12):1183-9.
Pentagastrin-induced sleep panic attacks: panic in the absence of elevated baseline arousal.

Geraci M, Anderson TS, Slate-Cothren S, Post RM, McCann UD.

Clinical Center Nursing Department, National Institutes of Health, Bethesda, Maryland, USA.

BACKGROUND: It has been suggested that pharmacological challenges that induce panic attacks are confounded by effects of environmental stress, elevated baseline arousal, and expectancy bias. METHODS: To control for effects of arousal and cognition on the panicogenic effects of pentagastrin, pharmacological challenges were conducted during sleep in seven patients with panic disorder or social phobia. All patients had previously experienced pentagastrin-induced panic while awake. Infusions of normal saline and pentagastrin (0.6 microg/kg) were administered in fixed order and timed so that pentagastrin infusions took place during the transition from Stage 2 to Stage 3 sleep. Long intravenous lines were placed for remote blood sampling and subsequent analysis of plasma adrenocorticotropic hormone and cortisol. Measures of anxiety and panic were obtained at baseline and upon awakening after pharmacological challenge. RESULTS: All seven subjects awoke within seconds following pentagastrin infusion. Four patients reported symptoms that met criteria for panic. Neither baseline anxiety nor neuroendocrine measures were predictive of panic. CONCLUSIONS: These data demonstrate the ability to induce panic during a period of diminishing arousal and indicate that panic attacks can occur in the absence of elevated arousal and environmental stress.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12488064&dopt=Abstract



J Biol Chem. 2002 Aug 30;277(35):32086-93. Epub 2002 Jun 13.
Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation.

Grishkovskaya I, Avvakumov GV, Hammond GL, Catalano MG, Muller YA.

Forschungsgruppe Kristallographie, Max-Delbruck-Centrum fur Molekulare Medizin, D-13092 Berlin, Germany.

The amino-terminal laminin G-like domain of human sex hormone-binding globulin (SHBG) contains a single high affinity steroid-binding site. Crystal structures of this domain in complex with several different steroid ligands have revealed that estradiol occupies the SHBG steroid-binding site in an opposite orientation when compared with 5 alpha-dihydrotestosterone or C19 androgen metabolites (5 alpha-androstan-3 beta,17 beta-diol and 5 alpha-androstan-3 beta,17 alpha-diol) or the synthetic progestin levonorgestrel. Substitution of specific residues within the SHBG steroid-binding site confirmed that Ser(42) plays a key role in determining high affinity interactions by hydrogen bonding to functional groups at C3 of the androstanediols and levonorgestrel and the hydroxyl at C17 of estradiol. Among residues participating in the hydrogen bond network with hydroxy groups at C17 of C19 steroids or C3 of estradiol, Asp(65) appears to be the most important. The different binding mode of estradiol is associated with a difference in the position/orientation of residues (Leu(131) and Lys(134)) in the loop segment (Leu(131)-His(136)) that covers the steroid-binding site as well as others (Leu(171)-Lys(173) and Trp(84)) on the surface of human SHBG and may provide a basis for ligand-dependent interactions between SHBG and other macromolecules. These new crystal structures have also enabled us to construct a simple space-filling model that can be used to predict the characteristics of novel SHBG ligands.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12065592&dopt=Abstract








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