Localisation and regulation of cholesterol transporters in the human hair follicle: mapping changes across the hair cycle

Abstract

Cholesterol has long been suspected of influencing hair biology, with dysregulated homeostasis implicated in several disorders of hair growth and cycling. Cholesterol transport proteins play a vital role in the control of cellular cholesterol levels and compartmentalisation. This research aimed to determine the cellular localisation, transport capability and regulatory control of cholesterol transport proteins across the hair cycle. Immunofluorescence microscopy in human hair follicle sections revealed differential expression of ATP-binding cassette (ABC) transporters across the hair cycle. Cholesterol transporter expression (ABCA1, ABCG1, ABCA5 and SCARB1) reduced as hair follicles transitioned from growth to regression. Staining for free cholesterol (filipin) revealed prominent cholesterol striations within the basement membrane of the hair bulb. Liver X receptor agonism demonstrated active regulation of ABCA1 and ABCG1, but not ABCA5 or SCARB1 in human hair follicles and primary keratinocytes. These results demonstrate the capacity of human hair follicles for cholesterol transport and trafficking. Future studies examining the role of cholesterol transport across the hair cycle may shed light on the role of lipid homeostasis in human hair disorders.

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

“… 205 , 250 , 279 , 282 , 310 , 319 , 322 , 324 , 326 , 328 , 330 - 335 , 337 - 340 , 342 , 343 In addition, an induction of SREBP1C / Srebp1c has also been observed. 336 , 342 Functionally, TO901317 increased cholesterol efflux, 250 , 259 , 260 , 262 , 264 , 282 , 319 , 324 , 329 , 331 , 342 decreased intracellular Aβ content, and increased Aβ secretion from different murine brain cells. 126 , 345 Further, it reduced Aβ 25-35 -mediated toxicity toward cells by induction of Abca1 .…”

“…Morevover, the cyclosporine A analog valspodar (PSC833) inhibited direct binding of radiolabeled cyclosporine A to ABCA1, revealing that valspodar also acts as an ABCA1 inhibitor. 245 , 282 Furthermore, several other calmodulin antagonists inhibited ABCA1-mediated cholesterol efflux and binding of APOA1. 245 These include pimecrolimus, 245 sirolimus, 245 and tacrolimus, 245 suggesting these molecules as potential scaffolds for the development of future ABCA1 modulators.…”

“… 205 , 245 , 250 , 252 , 259 , 260 , 262 , 264 , 271 , 272 , 279 , 280 , 282 , 308 , 310 , 317 , 319 , 322 , 324 , 326 , 328 - 345 TO901317 targeted both the LXR-α 250 , 310 , 328 , 330 , 332 , 335 , 337 - 340 , 342 and LXR-β pathways, 250 , 310 , 338 , 342 which correlated to ABCA1 / Abca1 induction on mRNA and ABCA1 protein levels. 205 , 250 , 279 , 282 , 310 , 319 , 322 , 324 , 326 , 328 , 330 - 335 , 337 - 340 , 342 , 343 In addition, an induction of SREBP1C / Srebp1c has also been observed. 336 , 342 Functionally, TO901317 increased cholesterol efflux, 250 , 259 , 260 , 262 , …”

“…Native/induced/selected cells naturally express the respective ABCA transporter or have been exposed to a ‘standard’ inducer, for example, the ABCA1 inducers 22-( R )-hydroxy-cholesterol, 122 , 205 , 249 , 252 , 259 , 262 - 264 , 268 , 277 , 278 , 305 - 315 TO901317, 205 , 245 , 250 , 252 , 259 , 260 , 262 , 264 , 271 , 272 , 279 , 280 , 282 , 308 , 310 , 317 , 319 , 322 , 324 , 326 , 328 - 345 or 8-Br-cAMP, 230 , 249 , 255 , 266 , 290 , 292 and overexpress the respective transporter in response ( e.g. , ABCA1).…”

“…Two groups of tracers have been established in terms of ABCA transporter function: (i) radiolabeled substrates, 250 , 272 , 305 , 306 , 338 , 339 , 354 , 364 , 366 , 393 , 395 , 404 , 419 , 511 , 512 , 136 , 222 , 230 , 245 , 249 , 253 , 255 , 259 , 260 , 262 , 264 , 265 , 267 - 270 , 273 , 276 , 278 , 289 - 292 , 311 , 313 , 315 , 318 , 329 , 341 , 367 , 377 , 381 , 384 , 385 , 464 , 467 , 499 , 513 and (ii) fluorescent substrates. 171 , 201 , 238 , 251 , 252 , 254 , 256 , 258 , 261 , 271 , 282 , 308 , 319 , 321 , ...…”