Oral sulfate transporters

A subtitle to this post is “Saliva sulfate is not a good surrogate for serum sulfate.” The very strange twist is that there are plenty of sulfate transporters along the dental line that may or may not be acting as sulfate transporters. This brings us back to the oral microbiome and a previous post on the mouth brain axis.

Saliva and sweat sulfate less than the serum [1]

Cole and Sandry and developed a controlled-flow anion chromatography technique to measure low concentrations of inorganic sulfate (SO₄) in human serum and cerebrospinal fluid. Their goal was to extend this technology to measuring low concentrations of sulfate in the sweat and saliva. The saliva had to be ultrafiltered to remove macromolecular polyanions that could bind irreversibly to their anion-exchange separator columns. Sweat was collected on filter pads applied to the forearm which was stimulated by pilocarpine iontophoresis.

• Saliva, 17 fasted volunteers 72 ± 4 μmol/1 (± S.E.);
• Sweat, 22 fasted volunteers, 83 ± 3 μ mol/1.
• Serum samples were reported to be significantly higher

A group from Hong Kong investigated changes in saliva anion concentration in patients who had undergone radiation therapy to treat nasopharyngeal carcinoma.

anion	BL	2 months	6 months	12 months	Time*
Chloride	27.31(16.81–42.78)	101.37(83.75–110.73)	94.77(74.05–113.59)	96.20(82.71–109.64)	<0.001
Nitrate	0.21(0.07–0.75)	0.07(0.04–0.20)	0.06(0.04–0.14)	0.07(0.04–0.13)	0.015
Phosphate	3.58(2.25–4.53)	3.74(3.11–5.26)	4.15(2.87–4.98)	3.77(3.38–6.13)	n.s.
Sulphate	0.10(0.08–0.16)	0.25(0.20–0.34)	0.22(0.16–0.31)	0.24(0.16–0.31)	<0.001
Thiocyanate	0.30(0.17–0.44)	0.08(0.00–0.20)	0.06(0.00–0.19)	0.08(0.00–0.27)	<0.001
Lactate	0.01(0.00–0.08)	0.31(0.03–0.56)	0.15(0.04–0.61)	0.13(0.03–0.66)	<0.001
Acetate	0.54(0.36–0.98)	0.68(0.41–0.92)	0.59(0.18–1.23)	0.51(0.22–0.87)	n.s.
Propionate	0.05(0.02–0.11)	0.07(0.02–0.15)	0.06(0.02–0.18)	0.07(0.02–0.12)	n.s.
Formate	0.01(0.01–0.05)	0.03(0.01–0.09)	0.04(0.01–0.07)	0.04(0.02–0.10)	0.011

Pow and coauthors also mentioned a decrease in saliva pH and a concern that this acidification could compromise oral health. A decrease in saliva flow is also a factor. Pow and coauthors named isothiocyanate, SCN^–, as part of the oral innate immune system against oral pathogens.

The active reabsorption of sulfate, as it occurs in the kidney, was not mentioned at all.

SlcA26A1 in oral mucosa

This image was produced from ProteinAtlas.org. According to Protein Atlas, Slc26A1 is found in the oral mucosa but not the salivary glands. The tongue was not analyzed. One the other hand, mRNA is found in the tongue.

Ameloblasts are oral epithelia derived cells that produce tooth enamal.

Slc26A acts as a sodium-independent DIDS-sensitive anion exchanger mediating bicarbonate, chloride, sulfate and oxalate transport. May play a role in the maintenance of the electrolyte and acid-base homeostasis in the kidney, by acting as a distal excretory segment-specific anion exchanger. Plays a major role in gastric acid secretion. Note that slc26a1 has similar functions according to UniProt.

Sulfate transporters at the forefront of enamal formation [3]

Michael Paine of the Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry of University of Southern California, Los Angeles, California, United States of America had a diverse group of collaborators in this study designed to understand pH regulation in enamel formation in a process called amelogenesis. [3]

For semi-quantifying the expression of Slc26a1, Slc26a6 and Slc26a7 mRNA, secretory-stage and maturation-stage RNA samples were obtained from the enamel organs of rat incisors. Four 4-week old Wistar Hannover rats, each weighing 100–110g, were sacrificed for their mandibles.[3]

1. The secretory stage involves synthesis and secretion of enamal matrix proteins by ameloblasts. The pH is near neutral.
2. The maturation phase involves acidification of the extracellular pH followed by a return to a near neutral pH. As inferred by the acidic pH, lysocomal enzymes are involved.

Slc26A1, 6, and 7 transcripts increased between the secretory to maturation phases. It should be noted that Slc26A2 had a good showing relative to the abundant house keeping protein β-actin in both phases. In the enamel maturation phase, both Slc26A6 and Slc26A7 had transcript levels relative to β-actin similar to that seen in the kidney. Slc26A1 levels were always similar to the kidney.

Gene symbol	Fold changes; rel β-actin	P values	ions transported
Slc26a1	39.8; 0.13 (0.032)	0.000031	sulfate-oxalate, sulfate-bicarbonate, sulfate-thiosulfate and oxalate-bicarbonate
Slc26a2	-1.2; 0.010 (0.0013)	0.368	sulfate, chloride, bicarb, oxalate
Slc26a3	1.2	0.391	chloride/bicarb
Slc26a4	1.0; 155.42 (1.81)	0.825	chloride-bicarbonate and chloride-formate
Slc26a5	1.1	0.711	sulfate, bicarb, chloride, oxalate
Slc26a6	5.4; 0.17 (0.076)	0.00016	sulfate, bicarb, chloride, oxalate
Slc26a7	7.8; 0.018 (0.016)	0.00013	sulfate, bicarb, chloride, oxalate
Slc26a8	1.1	0.8	sulfate, bicarb, chloride, oxalate
Slc26a9	-1.1; 0.00094 (0.00020)	0.263	sulfate, bicarb, chloride, oxalate
Slc26a10	N/A	N/A
Slc4a2	6.51 (1.74)		chloride-bicarb
Slc26a11	-1.5; 0.0013 (0.00051)	0.278	sulfate, lysosome
Slc11a2	0.011 (0.0017)		H+ metal cotransporter Cd2+ > Fe2+ > Co2+, Mn2+ >> Zn2+, Ni2+, VO2+
Slc36a	0.998 (0.00066)		proton/amino acid symporter with small apolar L-amino acids..samino acid derivatives GABA

• Sat, aka Slc26a1
• pendrin, aka slc26a4
• Pat, Slc, akaSlc26a6
• Sut2, aka, Slc26a7

Striae of Retzius, like tree ring research in austistic kids [4]?

Dental enamel is a structure that is formed as a result of the regular secretion by ameloblasts. These daily deposits of enamel become darker than normal. Several factors may cause these accentuated lines to become darker than normal:

• the stress of being born, i.e. the neonatal line
• fevers
• vaccinations, antibiotics
• infections of the mother during pregnancy.
• weaning stresses
• mineralization disturbances

If autistic children are just more stressed than neurotypical children, is this reflected in the number of accentuated lines?

Kurek and coauthors discussed cortisol and other factors that could influence both phases of enamel formation. Oral hygiene is an issue too. [4] Does stress affect transcription and/or post translational modification of any number of Slc26a family members that may or may not transport sulfate? An email was sent to Michael Paine [3] asking if he knew if the Slc26a members in ameloblasts transport sulfate. He doesn’t know. Does anyone? A 1969 study tracked radioactive sulfate and bromide in rats. Radioactivity could not be detected in the saliva. [5]

References

1. Cole DE, Landry DA. Determination of inorganic sulfate in human saliva and sweat by controlled-flow anion chromatography. Normal values in adult humans. J Chromatogr. 1985 Feb 8;337(2):267-78.
2. Pow EH, Chen Z, Kwong DL, Lam OL. Salivary Anionic Changes after Radiotherapy for Nasopharyngeal Carcinoma: A 1-Year Prospective Study. PLoS One. 2016 Mar 31;11(3):e0152817. PMC free article
3. Yin K, Lei Y, Wen X, Lacruz RS, Soleimani M, Kurtz I, Snead ML, White SN, Paine ML. SLC26A Gene Family Participate in pH Regulation during Enamel Maturation. PLoS One. 2015 Dec 15;10(12):e0144703. PMC free article
4. Kurek M, Borowska B, Lubowiedzka-Gontarek B, Rosset I, Żądzińska E. Disturbances in primary dental enamel in Polish autistic children. Sci Rep. 2020 Jul 29;10(1):12751 PMC free article
5. Barratt TM, Walser M. Extracellular fluid in individual tissues and in whole animals: the distribution of radiosulfate and radiobromide. J Clin Invest. 1969 Jan;48(1):56-66. PMC free article