Disease relevance of Clcn3

• ClC-3 chloride channel is upregulated by hypertrophy and inflammation in rat and canine pulmonary artery [1].
• In this study, we have shown that heterologous expression of ClC-3 in either Chinese hamster ovary (CHO-K1) or human hepatoma (Huh-7) cells results in the formation of large, acidic vesicular structures within cells [2].
• This study is the first to demonstrate changes in mRNA levels of HCN2, HCN4, and ClC-3 in cardiac hypertrophy induced by abdominal aortic banding [3].
• Treatment with the antioxidant, Trolox (2 mg/kg body weight), prevented the initial increase in ClC-3 and Na(+)/Ca(2+) exchanger proteins [4].
• The up-regulation of ClC-3 and Na(+)/Ca(2+) exchanger proteins during the early stages of diabetes and its prevention by antioxidants suggests that the proteins regulating ion transport may have a pathophysiological role in the development of diabetic cataracts [4].

High impact information on Clcn3

• A detailed analysis revealed that ClC-3 was expressed by type B intercalated cells, whereas ClC-5 was expressed by type A intercalated cells [5].
• Biophysical properties of ClC-3 differentiate it from swelling-activated chloride channels in Chinese hamster ovary-K1 cells [6].
• These data suggest that ClC-3 cannot be responsible for the swelling-activated chloride channel under all circumstances [6].
• However, recent studies have shown that native ClC-3 in hepatocytes is primarily intracellular [6].
• Whereas ClC-5 is localized intracellularly, ClC-3 has been reported to be a swelling-activated plasma membrane channel [6].

Biological context of Clcn3

• However, the amino acid sequence was weakly homologous to those of other ClC Cl- channels except for ClC-3, which we recently identified as a Ca2+-sensitive ORCC [7].
• Cl- channels have been implicated in essential cellular functions including volume regulation, progression of cell cycle, cell proliferation and contraction, but the physiological functions of the ClC-3 channel are controversial [1].
• In conclusion, upregulation of ClC-3 in rat hypertensive lung and heart is a novel observation [1].
• Adenovirus-mediated delivery and overexpression of ClC-3 in canine PASMCs improved cell viability against increasing concentrations of hydrogen peroxide (H2O2, range 50-250 microM) [1].
• 6. Polymerase chain reaction followed by DNA sequence analysis indicated the presence of mRNA homologous to the ClC-3 chloride channel in pancreatic tissue from 5-day-old rats [8].

Anatomical context of Clcn3

• Our functional data suggest that upregulation of ClC-3 is an adaptive response of inflamed pulmonary artery, which enhances the viability of PASMCs against reactive oxygen species [1].
• Reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and Western immunoblot analysis indicated that histopathological alterations were associated with upregulation of the ClC-3 mRNA and protein expression in both smooth muscle cells of hypertensive pulmonary arteries and in cardiac myocytes [1].
• ClC-3 is strongly expressed in the apical membrane of principal cells of the caput epididymidis and the vas deferens and is less abundant in principal cells of the body and cauda epididymidis [9].
• Detection of ClC-3 and ClC-5 in epididymal epithelium: immunofluorescence and RT-PCR after LCM [9].
• Western blot and immunofluorescence analysis demonstrated that ClC-3 and ClC-5 proteins are present in all regions of the epididymis and in the vas deferens [9].

Associations of Clcn3 with chemical compounds

• Changes in mRNA levels of HCN2, HCN4, and ClC-3 were alleviated by both candesartan and amlodipine, and these levels of the treated groups were not different from those in the sham control group [3].
• These results suggest that ClC-2, ClC-3 and ICln either participate in taurine transport themselves or upregulate an endogenous oocyte osmolyte channel [10].

Physical interactions of Clcn3

• These findings are consistent with a potential role for ClC-3 in transepithelial chloride transport by principal cells and for ClC-5 in the acidification of H(+)-ATPase-containing vesicles in narrow and clear cells [9].

Other interactions of Clcn3

• Three new members, named ClC-K1, ClC-K2, ClC-3, have been isolated [11].
• 1. The expression of ClC-3 was examined in rat lacrimal gland and submandibular salivary gland cells using RT-PCR and Western analysis [12].
• The levels of ClC-2 in both atria and ventricles were significantly less than those measured for ClC-3 (n = 3; P < 0.05) [13].
• RT-PCR revealed the presence of transcripts of ClC-1, ClC-2 and ClC-3, which were verified by DNA sequencing [14].
• This study investigates changes in the messenger RNA (mRNA) expression levels of HCN2 and HCN4 encoding rat If channels; ClC-3, a candidate gene for swelling-activated Cl- channel, and pICln, a regulatory subunit of Cl- channels in rat hypertrophied heart induced by banding the abdominal aorta [3].

Analytical, diagnostic and therapeutic context of Clcn3

• Immunofluorescence and immunoblots localized native ClC-3 preferentially but not exclusively to the canalicular membrane [15].
• 2. Expression of mRNA encoding ClC-3, and ClC-3 protein, was found in rat submandibular gland by RT-PCR and Western analysis [12].
• On the other hand, both size exclusion chromatography and sedimentation equilibrium analysis show that C-ClC-3 exists as a monomer in solution, not a dimer like the whole ClC-3 molecule [16].
• Also, mRNA for ClC-3 was determined by Northern blot analysis [4].

References