[show abstract][hide abstract] ABSTRACT: Expressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO(2), AQP9-null mice suffer reduced survival rates (LD(50), 12 mg/kg) compared with WT mice (LD(50), 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10-20 times more arsenic than WT mice. Within hours after NaAsO(2) injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only approximately 10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity.
Proceedings of the National Academy of Sciences 09/2009; 106(37):15956-60. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aquaporin 6 (AQP6) is an anion channel that is expressed primarily in acid secreting alpha-intercalated cells of the kidney collecting duct. In addition, AQP6 anion channel permeability is gated by low pH. Inspection of the N-terminus of AQP6 revealed a putative calmodulin binding site. AQP6-expressing CHO-K1 cell lysates were mixed with calmodulin beads and AQP6 was pulled down in the presence of calcium. Mutagenesis of the N-terminal calmodulin binding site in full length mouse AQP6 resulted in a loss of calmodulin binding activity. Mouse and human AQP6 calmodulin binding site peptides bound dansyl-calmodulin with a dissociation constant of approximately 1microM. The binding of AQP6 to calmodulin may be an important key to determining the physiological role of AQP6 in the kidney.
Biochemical and Biophysical Research Communications 04/2009; 383(1):54-7. · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Osteoclasts are cells specialized for bone resorption and play important roles in bone growth and calcium homoeostasis. Differentiation of osteoclasts involves fusion of bone marrow macrophage mononuclear precursors in response to extracellular signals. A dramatic increase in osteoclast cell volume occurs during osteoclast biogenesis and is believed to be mediated by AQP9 (aquaporin 9), a membrane protein that can rapidly transport water and other small neutral solutes across cell membranes.
In the present study we report an increase in expression of AQP9 during differentiation of a mouse macrophage cell line into osteoclasts. Bone marrow macrophages from wild-type and AQP9-null mice differentiate into osteoclasts that have similar morphology, contain comparable numbers of nuclei, and digest synthetic bone to the same extent. Bones from wild-type and AQP9-null mice contain similar numbers of osteoclasts and have comparable density and structure as measured by X-ray absorptiometry and microcomputed tomography.
Our results confirm that AQP9 expression rises during osteoclast biogenesis, but indicate that AQP9 is not essential for osteoclast function or differentiation under normal physiological conditions.
Biology of the Cell 08/2008; 101(3):133-40. · 3.49 Impact Factor