Organic cation/carnitine transporter, OCTN2, transcriptional activity is regulated by osmotic stress in epididymal cells

Abstract

Protection of cells from osmotic stress is crucial for their survival. Exposure to high osmolarity promotes rapid diffusion of water across cell membranes, dramatically increasing cellular ionic strength, leading to disruption of key proteins/DNA resulting in cell-cycle arrest and apoptosis. The luminal microenvironment of the epididymis is hypertonic; therefore, epididymal cells adapt to the higher osmolarity by accumulating organic osmolytes, such as L-carnitine. Osmolytes do not perturb cells when accumulated in high concentrations, nor do they affect key proteins or damage DNA. Therefore, osmolytes and their transporters are crucial for cell survival. Transporters that are responsible for the accumulation of organic osmolytes have been shown to be regulated at the transcriptional level by hypertonicity. The present study examines the gene expression of known osmoprotective/stress genes in epididymal cells exposed to changes in tonicity. We demonstrate that the osmoprotective/stress pathways present in other organs, such as the kidney, operate in the epididymis, potentially aiding in the protection of its luminal cells and spermatozoa. Further, it was also seen that OCTN2, a transporter that is thought to be responsible for the accumulation of L-carnitine in the epididymal lumen, is regulated in response to changes in tonicity.

Carnitine Traffic in Cells. Link With Cancer

“…The sperm maturation requires a high amount of carnitine that is accumulated in epididymal cells from blood, thanks to OCTN2 (Figure 2). Then, carnitine is released in the epididymal lumen via CT2 (Jeulin and Lewin, 1996;Enomoto et al, 2002;Cotton et al, 2010) where its measured concentration reaches 50-100 mM (Figure 2). In good agreement with this role, carnitine supply to patients with asthenozoospermia results in an increase of sperm motility.…”

NHERF2/NHERF3 Protein Heterodimerization and Macrocomplex Formation Are Required for the Inhibition of NHE3 Activity by Carbachol

“…NHERF1, NHERF2, and NHERF3 are primarily localized to the brush border (2,4,5). The NHERF family was named because of its functions in the regulation of NHE3, which is a Na ϩ /H ϩ antiporter expressed in the brush border of kidney proximal tubules and the gastrointestinal system.…”

Pharmacological and pathophysiological roles of carnitine/organic cation transporters (OCTNs: SLC22A4, SLC22A5 and Slc22a21)

“…This may be explained by the following mechanisms: OCTN2‐mediated sodium ion‐dependent active transport imports carnitine from the blood into epithelial cells, from which it is released to the lumen via the sodium ion‐independent CT2 transporter. However, in mice Octn2 is localized to the luminal membrane of epididymal epithelial cells, particularly the distal corpus and cauda . There may be several reasons for this, including the presence of splice variants and species difference.…”