Ask about this productRelated genes to: LRRC8A antibody
- Gene:
- LRRC8A NIH gene
- Name:
- leucine rich repeat containing 8 VRAC subunit A
- Previous symbol:
- LRRC8
- Synonyms:
- KIAA1437, FLJ10337, SWELL1
- Chromosome:
- 9q34.11
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-26
- Date modifiied:
- 2019-04-23
Related products to: LRRC8A antibody
Related articles to: LRRC8A antibody
- Traumatic brain injury (TBI) is a significant concern, with millions sustaining a TBI each year. The vast majority are categorized as mild, in which diffuse pathologies are the hallmark and multiple cell types are affected, including astrocytes. Buprenorphine (bup), a semi-synthetic opioid, is a common human and veterinary analgesic. Previous studies from our group showed that a single dose of slow-release bup administered acutely following TBI alters astrocyte morphology at 1 day and 4 weeks post-injury in a region-specific manner. The current study expands on these findings by examining how four major astrocyte-associated proteins, GFAP, SWELL1/LRRC8A, TRPM4, and AQP4, are affected by such a dose of bup. Adult male rats received either sham or TBI via a central fluid percussion injury model, followed by saline or bup 15 min following injury. Protein quantification at 1 day and 4 weeks post-injury revealed region- and time-dependent effects of acute bup administration. Specifically, bup reduced hippocampal GFAP, increased cortical TRPM4, and elevated thalamic AQP4 and SWELL1 at 4 weeks following TBI. Taken together, these findings indicate that a single post-injury dose of bup can alter major astrocytic protein expression beyond the acute phase in a region- and time-dependent manner. - Source: PubMed
Publication date: 2026/03/30
Lilova Radina LBernas TytusRyu JaneKelliher CorrinaLafrenaye Audrey - Pancreatic beta cells have the unique function of synthesizing and secreting high amounts of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). The mechanism of GABA secretion, whether vesicular or channel-mediated, is debated. Our study reveals surprising temporal complexity in the pattern of islet GABA secretion. We used insulin secretion modulators to demonstrate that GABA release is not directly correlated with insulin secretion. VGAT reporter mice also showed that beta cells do not express the requisite vesicular GABA transporter (VGAT) for vesicular GABA release. Instead, GABA is secreted from the cytosol in pulses by the LRRC8A/D isoform of the volume regulatory anion channel (VRAC). We further demonstrate the dynamic coordination of GABA release with calcium influx in beta cells and dependence on beta cell depolarization. These results suggest a model where GABA is released during the peaks of beta cell calcium oscillations to provide feedback which strengthens and reinforces the oscillation waveform. - Source: PubMed
Publication date: 2026/04/03
Stis Austin ELazimi Charles SFerreira Sandra MCuaycal Alexandra ESmurlick DylanHagan D WalkerNakayama TaylorGandhi Sunil PSmith EmerySpicer Timothy PPhelps Edward A - Volume-activated chloride current (VACC), the most common and abundant anion current in organisms, is involved in various physiological and pathological processes. However, its expression and characteristics in preadipocytes remain unclear. Whole-cell patch clamp technique was used to investigate the presence and properties of VACC in 3T3-L1 preadipocytes, as well as the effects of chloride channel blockers (NPPB, DIDS, and tamoxifen) on this current under different osmotic conditions. Additionally, 3T3-L1 preadipocytes were treated with the chloride channel blocker TMEM16A to observe its effect on cell differentiation. Hypotonic stimulation significantly induced whole-cell currents in 3T3-L1 preadipocytes, which exhibited obviously outward-rectifying and volume-activated characteristics. Under hypotonic stimulation, NPPB, DIDS, and tamoxifen all inhibited the current, with NPPB showing a significantly stronger inhibitory effect than DIDS and tamoxifen. Moreover, growth-arrested 3T3-L1 preadipocytes at 2 days post-confluence were successfully induced, with mRNA levels of C/EBPα, C/EBPβ, PPARγ and FABP4 peaking on day 3 and decreasing by day 14. Protein levels of PPARγ, perilipin 1 and LRRC8A were significantly upregulated during differentiation. Treatment with TMEM16A significantly reduced adipocyte lipid droplet formation and FABP4 mRNA/protein levels, but increased C/EBPα and PPARγ mRNA levels, as well as LRRC8A protein levels after 3 days. Collectively, our results clarify the characteristics of VACC in 3T3-L1 preadipocytes, confirm the inhibitory effect of chloride channel blockers on 3T3-L1 preadipocyte differentiation, fill the gap in the understanding of VACC in preadipocytes, and lay a preliminary experimental foundation for further exploring the role of VACC in adipocyte differentiation. - Source: PubMed
Publication date: 2026/04/07
Guan HuaHuang ZhenghaoWang ZiyueXiang AoqiZhang LushaChen XiaochangSu PeihongWang RuiZhang HaifengYu Qi - Leucine-rich repeat-containing 8A (LRRC8A; also known as SWELL1), the essential subunit of volume-regulated anion channels (VRACs), is amplified in multiple malignancies and has been implicated in tumor progression and therapeutic resistance. Three-dimensional (3D) cancer spheroids have been well-established as in vitro models that recapitulate characteristics of tumor stemness and intrinsic drug resistance. In the present study, spheroid formation in human breast cancer cell lines, YMB-1 and MDA-MB-468, conferred resistance to multiple anticancer drugs, including doxorubicin (DOX), gemcitabine (GEM), and 5-fluorouracil (5-FU), thereby mimicking the characteristic properties of breast cancer stem-like cells. LRRC8A expression was upregulated in 3D spheroids compared with adherent 2D monolayers, and its pharmacological inhibition induced membrane hyperpolarization accompanied by intracellular Cl accumulation. Inhibition of LRRC8A significantly sensitized spheroids to DOX, GEM, and 5-FU. Spheroid formation increased the expression of multidrug resistance-related protein 3 (MRP3) and the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4), whereas LRRC8A inhibition suppressed their expression. The transcriptional upregulation of MRP3 and CYP3A4 was mediated through the NRF2-CEBPB/D transcriptional axis. Collectively, these findings suggest that LRRC8A inhibition may represent a therapeutic strategy to overcome chemoresistance by repressing MRP3 and/or CYP3A4 expression in breast cancer stem cells. - Source: PubMed
Publication date: 2026/03/13
Otsuka RyoKajikuri JunkoMatsui MikiKito HiroakiKitahara AyanoMitsui HinakoYamaguchi YoheiHisada TomokaToyama TatsuyaOhya Susumu - - Source: PubMed
Publication date: 2026/03/27
Jie LingjunFeng BaolongZhou YufanDu ChanZhou WenlinZhang RuonanShen WeiChen JiajinWu PenglongKong XuZhan YuliangShi MeimeiLi GuiyangLi LeiPan LeiZhang Yanhui