Heiner Max

A Functional ABCC11 Allele Is Essential in the Biochemical Formation of Human Axillary Odor

The characteristic human axillary odor is formed by bacterial action on odor precursors that originate from apocrine sweat glands. Caucasians and Africans possess a strong axillary odor ,whereas many Asians have only a faint acidic odor. In this study, we provide evidence that the gene ABCC11 (MRP8), which encodes an apical efflux pump, is crucial for the formation of the characteristic axillary odor and that a single-nucleotide polymorphism (SNP) 538G --> A, which is prominent among Asian people, leads to a nearly complete loss of the typical odor components in axillary sweat. The secretion of amino-acid conjugates of human-specific odorants is abolished in homozygotic carriers of the SNP, and steroidal odorants and their putative precursors are significantly reduced. Moreover, we show that ABCC11 is expressed and localized in apocrine sweat glands. These data point to a key function of ABCC11 in the secretion of odorants and their precursors from apocrine sweat glands. SNP 538G --> A, which also determines human earwax type, is present on an extended haplotype, which has reached >95% frequency in certain populations in recent human evolution. A strong positive selection in mate choice for low-odorant partners with a dysfunctional ABCC11 gene seems a plausible explanation for this striking frequency of a loss-of-function allele.

Characterization of peptides bound to extracellular and intracellular HLA-DR1 molecules

Exogenous antigens are internalized by antigen-processing cells and processed within vesicular compartments to produce antigenic peptides that bind to newly synthesized MHC II molecules. These MHC class II peptide complexes are displayed at the plasma membrane and stimulate specific CD4+ T cells. In the present study, we established a method to isolate intracellular MHC molecules in a preparative scale (2-3 mg HLA-DR1) from endosomal compartments by Percoll density-gradient centrifugation. Peptides associated with HLA-DR1 in these intracellular fractions were released, purified by microbore HPLC, characterized by sequencing, and compared with the amino acid composition of peptides derived from MHC class II molecules obtained by solubilization of the plasma membrane. The binding affinity of these MHC fractions was analyzed by our highly sensitive binding assay using different DR1-restricted IM and Ii peptides. The results indicate that (a) intracellular MHC molecules show higher peptide-binding capacity, (b) peptides that are about 18-25 amino acids long need only a core region of 11 amino acids for binding, (c) specific positions of the peptides are important for DR1 binding, (d) most of the naturally processed peptides show a proline at position 2 or 3 that may represent a stop signal for trimming, and (e) Ii peptides are very abundant in DR1 peptide pools derived from intracellular compartments.

Glutathione‐conjugated sulfanylalkanols are substrates for ABCC11 and γ‐glutamyl transferase 1: a potential new pathway for the formation of odorant precursors in the apocrine sweat gland

We have previously shown that precursors of odorous components characteristic of axillary sweat are hardly detectable or undetectable in individuals carrying the 538G > A SNP in the ABCC11 transporter gene. However, it is unclear, whether ABCC11 is directly involved in the transport of these compounds. To approach this question, transport of peptide‐conjugated potential precursors of 3‐methyl‐3‐sulfanylhexanol (3M3SH), a key determinant of axillary malodour, was measured using membrane vesicles of Sf9 insect cells overexpressing human ABCC11. Whilst no ABCC11‐mediated transport was detected for the dipeptide precursor Cys‐Gly‐3M3SH, the glutathione conjugate of 3M3SH (SG‐3M3SH) was robustly taken up by ABCC11 at a transport rate of 0.47 pmol/mg/min. Collectively, these results illuminate SG‐3M3SH as a putative precursor of 3M3SH, which then may undergo intra‐vesicular maturation to generate Cys‐Gly‐3M3SH. Critically, the apocrine sweat gland was demonstrated to express γ‐glutamyl transferase 1 (GGT1) protein, which is known to catalyse the deglutamylation of glutathionyl conjugates. Additionally, we provide evidence that recombinant and isolated hepatic human GGT1 is capable of transforming SG‐3M3SH to Cys‐Gly‐3M3SH in vitro. To sum up, we demonstrate that the functionality of ABCC11 is likely to play an important role in the generation of axillary malodour. Furthermore, we identify GGT1 as a key enzyme involved in the biosynthesis of Cys‐Gly‐3M3SH.

Alpha‐Glucosylrutin: ein hochwirksames Flavonoid zum Schutz vor oxidativem Streß

Das Bioflavonoid alpha‐Glucosylrutin (AGR) findet aufgrund seiner starken antioxidativen Wirksamkeit und hohen epidermalen Bioverfügbarkeit zunehmend Verwendung im dermato‐kosmetischen Bereich. Bioflavonoide sind sekundäre Pflanzenstoffe (Phytamine) mit einer gemeinsamen chemischen Grundstruktur und einem breit gefächerten Wirkungsspektrum, vor allem aber der Fähigkeit, reaktive Sauerstoffspezies (reactive oxygen species, ROS) zu neutralisieren. ROS beeinflussen und schädigen die Zelle sowohl durch direkte zytotoxische Effekte (Membrandestruktion durch Induktion radikalischer Kettenreaktionen, Mutationen nukleärer und mitochondrialer DNA etc.) als auch indirekt durch Modifikation intrazellulärer Signaltransduktionskaskaden, die entzündliche und proliferative Prozesse regulieren. Die ausgezeichnete antioxidative Wirksamkeit von AGR konnte durch verschiedene experimentelle in‐vitro‐ und in‐vivo‐Untersuchungen bestätigt werden. Weiterführende klinische Studien belegen eindeutig die Wirksamkeit einer prophylaktischen Anwendung von AGR bei dermatologischen Krankheitsbildern wie der polymorphen Lichtdermatose (PLD), bei denen oxidativer Streß von pathogenetischer Relevanz ist. Auch in anderen dermato‐kosmetischen Indikationsbereichen wie der vorzeitigen (lichtbedingten) Hautalterung scheint eine vorbeugende Behandlung mit AGR vielversprechend zu sein. In allen durchgeführten in‐vivo‐Untersuchungen zeigte sich zudem, daß AGR in den verwendeten Konzentrationen ein sehr gut hautverträglicher Wirkstoff für die medizinische Hautpflege ist.

Hair and stress: A pilot study of hair and cytokine balance alteration in healthy young women under major exam stress

Mouse models show that experimental stress mimicking prolonged life-stress exposure enhances neurogenic inflammation, induces adaptive immunity cytokine-imbalance characterized by a shift to Type 1 T-helper cell cytokines and increases apoptosis of epithelial cells. This affects hair growth in otherwise healthy animals. In this study, we investigate whether a prolonged naturalistic life-stress exposure affects cytokine balance and hair parameters in healthy humans. 33 (18 exam, 15 comparison) female medical students with comparable sociobiological status were analyzed during a stressful final examination period, at three points in time (T) 12 weeks apart. T1 was before start of the learning period, T2 between the three-day written exam and an oral examination, and T3 after a 12 week rest and recovery from the stress of the examination period. Assessments included: self-reported distress and coping strategies (Perceived Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress [TICS]), COPE), cytokines in supernatants of stimulated peripheral blood mononucleocytes (PBMCs), and trichogram (hair cycle and pigmentation analysis). Comparison between students participating in the final medical exam at T2 and non-exam students, revealed significantly higher stress perception in exam students. Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and hair parameters changed significantly from T1 to T2 in the exam group, but not the control. However, no group differences were found for cytokine balance or hair parameters at T2. The study concludes that in humans, naturalistic stress, as perceived during participation in a major medical exam, has the potential to shift the immune response to TH1 and transiently hamper hair growth, but these changes stay within a physiological range. Findings are instructive for patients suffering from hair loss in times of high stress. Replication in larger and more diverse sample populations is required, to assess suitability of trichogram analysis as biological outcome for stress studies.

Efficacy of a New Tonic Containing Urea, Lactate, Polidocanol, and Glycyrrhiza inflata Root Extract in the Treatment of a Dry, Itchy, and Subclinically Inflamed Scalp

Background/Aims: Dry, itchy and inflamed scalp conditions are common and often associated with diseases such as atopic dermatitis or psoriasis. To improve these symptoms, we investigated the efficacy of a new tonic containing the active ingredients urea, lactate, polidocanol, and Glycyrrhiza inflata root extract, containing licochalcone A. Study Design/Methods: 30 subjects with dry and itchy scalp conditions underwent a randomized half-head study for 4 weeks, applying the leave-on tonic three times a week on one side of the scalp. Tonic effects on skin hydration, itching, lipids, microinflammation, and substantivity of tonic compounds were determined using corneometry, middle-infrared spectroscopy, direct analysis in real-time mass spectrometry, and enzyme-linked immunosorbent assay. Volunteers performed a self-assessment; changes in scalp condition were documented by in vivo microscopy. Results: After tonic treatment, scalp moisture was significantly increased, whereas scalp itching and tautness were significantly reduced. Results also demonstrated a high substantivity of urea and lactate on the scalp, an increase in triglyceride, and a decrease in free fatty acid levels. The amount of total lipids was unchanged. Analyses of scalp wash-ups verified a significant reduction in important pro-inflammatory markers. Conclusion: Due to the actives urea, lactate, polidocanol, and the anti-inflammatory licochalcone A, the new scalp tonic exhibited excellent performance in alleviating scalp dryness, itching, microinflammation, and in normalizing disturbances of scalp lipids.

ABCC11 – as key anti-odor target

Background In a previous publication, we showed that the ABCC11 transporter is crucial for the formation of the characteristic axillary odor and that a 538G>A single nucleotide polymorphism (SNP) in the gene, prominent in Asians, leads to a nearly complete loss of the typical sweat odor components in these carriers. As it is unclear, whether ABCC11 is directly involved in the transport of these components, we performed ABCC11-mediated transporter experiments with various potential odor precursors and also studied possible pathways for the formation of these precursors.

Effective axillary malodour reduction by polyquaternium‐16‐containing deodorants

Worldwide, individuals apply deodorants to combat malodour formation originating from the axillary vault. Considering the globally increasing demand for efficacious, safe deodorants, we investigated the antimicrobial effectiveness of a polymeric quaternary ammonium compound (PQ‐16) as a new active in a roll‐on formulation against microbial growth and axillary malodour.