Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS wh...Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS who presented with diffuse and treatment-resistant progressive hair loss and were diagnosed with FAGA were included in the study. 25 patients who were diagnosed with female androgenetic alopecia but did not have PCOS were considered as the control group. PCOS and control groups were matched by age. Follicular miniaturization, displacement of terminal hairs with vellus hairs, and a diffuse decrease in hair density were accepted as FAGA in the trcihoscopy examination of the vertex and bitempoaral area. On the third day of the menstrual cycle serum FSH, LH, testosterone, PRL and insulin levels were measured. Insulin resistance was calculated with HOMA-IR. Serum pannexin-1 channel levels of each group were mesured with ELISA. Results: Serum pannexin 1 channels levels of FAGA group due to PCOS were found to be significantly higher than FAGA patients in the control group (2.72 ± 1.09 ng/mL vs 1.65 ± 0.97 ng/mL, p < 0.01). Serum LH, insulin and testosterone levels of PCOS group were significantly higher than controls. HOMA-IR values were significantly higher and >2.5 in the PCOS group compared to the controls. PRL values were similar except for one patient with elevated PRL. Serum FSH values were the same in both groups. A positive and significant correlation was found between pannexin 1 channels levels and HOMA-IR and serum testosterone levels (r = 0.650, p Conclusions: In addition to hyperandrogenemia, increased pannexin 1 channel levels may play a role in the etiology of PCOS associated FAGA, as it impairs the communication between the skin and hair follicle.展开更多
Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms thr...Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms three species, GLY0, GLY1, and GLY2. Here, we describe four independent families in which mutations in PANX1 cause familial or sporadic female infertility via a phenotype that we term “oocyte death.” The mutations, which are associated with oocyte death, alter the PANX1 glycosylation pattern, influence the subcellular localization of PANX1 in cultured cells, and result in aberrant PANX1 channel activity, ATP release in oocytes, and mutant PANX1 GLY1. Overexpression of a patient-derived mutation in mice causes infertility, recapitulating the human oocyte death phenotype. Our findings demonstrate the critical role of PANX1 in human oocyte development, provide a genetic explanation for a subtype of infertility, and suggest a potential target for therapeutic intervention for this disease.展开更多
AIM: To evaluate plasma and aqueous levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.METHODS: The study included three age and gendermatched groups of 20 cataract patients with no...AIM: To evaluate plasma and aqueous levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.METHODS: The study included three age and gendermatched groups of 20 cataract patients with no diabetes or additional disease(Group C), 20 cataract patients with diabetes and no retinopathy(Group DM+C), and 20 cataract patients with diabetic retinopathy(Group DR+C).All the patients were examined with respect to body mass index(BMI), fasting plasma glucose, hemoglobin A1c(HbA1c), and lipid profile.Phacoemulsification and intraocular lens(Phaco+IOL) implantation were performed to all patients in all the groups, and aqueous samples were taken during the operation.The plasma and aqueous adiponutrin and pannexin 1 levels were analyzed using enzyme-linked immunosorbent assays.RESULTS: A statistically significant difference was determined between the groups with respect to BMI, fasting plasma glucose, and HbA1c levels(P<0.05 for all parameters tested).The plasma adiponutrin levels of Group DR+C were statistically significantly lower than those of Group C and Group DM+C(P<0.001, P=0.004).No statistically significant difference was determined in the aqueous adiponutrin levels in three groups.The plasma pannexin 1 levels of Groups DM+C and DR+C were statistically significantly lower than those of Group C(both P=0.001).The aqueous pannexin 1 levels of Group DR+C were statistically significantly higher than those of Group C and Group DM+C(P=0.001, P<0.001).CONCLUSION: Adiponutrin and pannexin 1, which play an important role in the pathophysiology of diabetes and obesity, and have a regulatory role in hyperglycemia and insulin resistance.The measurement of adiponutrin and pannexin 1 levels may support clinicians in determining the risk of DR development.展开更多
Pannexin 1(Panx 1),as a large-pore membrane channel,is highly permeable to ATP and other signaling molecules.Previous studies have demonstrated the expression of Panx 1 in the nervous system,including astrocytes,micro...Pannexin 1(Panx 1),as a large-pore membrane channel,is highly permeable to ATP and other signaling molecules.Previous studies have demonstrated the expression of Panx 1 in the nervous system,including astrocytes,microglia,and neurons.However,the distribution and function of Panx 1 in the peripheral nervous system are not clear.Blocking the function of Panx 1 pharmacologically(carbenoxolone and probenecid)or with small interfering RNA targeting pannexins can greatly reduce hypotonicity-induced ATP release.Treatment of Schwann cells with a Ras homolog family member(Rho)GTPase inhibitor and small interfering RNA targeting Rho or cytoskeleton disrupting agents,such as nocodazole or cytochalasin D,revealed that hypotonicity-induced ATP release depended on intracellular RhoA and the cytoskeleton.These findings suggest that Panx 1 participates in ATP release in Schwann cells by regulating RhoA and the cytoskeleton arrangement.This study was approved by the Animal Ethics Committee of Nantong University,China(No.S20180806-002)on August 5,2018.展开更多
We recently reported that targeted deletion of Pannexin 1 in neural precursor cells of the ventricular zone impairs the maintenance of these cells in healthy and stroke-injured brain. Here we frame this exciting new f...We recently reported that targeted deletion of Pannexin 1 in neural precursor cells of the ventricular zone impairs the maintenance of these cells in healthy and stroke-injured brain. Here we frame this exciting new finding in the context of our previous studies on Pannexin 1 in neural precursors as well as the close rela- tionship between Pannexin 1 and purinergic receptors established by other groups. Moreover, we identify important gaps in our understanding of Pannexin 1 in neural precursor cell biology in terms of the under- lying molecular mechanisms and functional/behavioural outcomes.展开更多
文摘Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS who presented with diffuse and treatment-resistant progressive hair loss and were diagnosed with FAGA were included in the study. 25 patients who were diagnosed with female androgenetic alopecia but did not have PCOS were considered as the control group. PCOS and control groups were matched by age. Follicular miniaturization, displacement of terminal hairs with vellus hairs, and a diffuse decrease in hair density were accepted as FAGA in the trcihoscopy examination of the vertex and bitempoaral area. On the third day of the menstrual cycle serum FSH, LH, testosterone, PRL and insulin levels were measured. Insulin resistance was calculated with HOMA-IR. Serum pannexin-1 channel levels of each group were mesured with ELISA. Results: Serum pannexin 1 channels levels of FAGA group due to PCOS were found to be significantly higher than FAGA patients in the control group (2.72 ± 1.09 ng/mL vs 1.65 ± 0.97 ng/mL, p < 0.01). Serum LH, insulin and testosterone levels of PCOS group were significantly higher than controls. HOMA-IR values were significantly higher and >2.5 in the PCOS group compared to the controls. PRL values were similar except for one patient with elevated PRL. Serum FSH values were the same in both groups. A positive and significant correlation was found between pannexin 1 channels levels and HOMA-IR and serum testosterone levels (r = 0.650, p Conclusions: In addition to hyperandrogenemia, increased pannexin 1 channel levels may play a role in the etiology of PCOS associated FAGA, as it impairs the communication between the skin and hair follicle.
文摘Connexins and pannexins are two protein families that play an important role in cellular communication. Pannexin 1 (PANX1), one of the members of pannexin family, is a channel protein. It is glycosylated and forms three species, GLY0, GLY1, and GLY2. Here, we describe four independent families in which mutations in PANX1 cause familial or sporadic female infertility via a phenotype that we term “oocyte death.” The mutations, which are associated with oocyte death, alter the PANX1 glycosylation pattern, influence the subcellular localization of PANX1 in cultured cells, and result in aberrant PANX1 channel activity, ATP release in oocytes, and mutant PANX1 GLY1. Overexpression of a patient-derived mutation in mice causes infertility, recapitulating the human oocyte death phenotype. Our findings demonstrate the critical role of PANX1 in human oocyte development, provide a genetic explanation for a subtype of infertility, and suggest a potential target for therapeutic intervention for this disease.
文摘AIM: To evaluate plasma and aqueous levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.METHODS: The study included three age and gendermatched groups of 20 cataract patients with no diabetes or additional disease(Group C), 20 cataract patients with diabetes and no retinopathy(Group DM+C), and 20 cataract patients with diabetic retinopathy(Group DR+C).All the patients were examined with respect to body mass index(BMI), fasting plasma glucose, hemoglobin A1c(HbA1c), and lipid profile.Phacoemulsification and intraocular lens(Phaco+IOL) implantation were performed to all patients in all the groups, and aqueous samples were taken during the operation.The plasma and aqueous adiponutrin and pannexin 1 levels were analyzed using enzyme-linked immunosorbent assays.RESULTS: A statistically significant difference was determined between the groups with respect to BMI, fasting plasma glucose, and HbA1c levels(P<0.05 for all parameters tested).The plasma adiponutrin levels of Group DR+C were statistically significantly lower than those of Group C and Group DM+C(P<0.001, P=0.004).No statistically significant difference was determined in the aqueous adiponutrin levels in three groups.The plasma pannexin 1 levels of Groups DM+C and DR+C were statistically significantly lower than those of Group C(both P=0.001).The aqueous pannexin 1 levels of Group DR+C were statistically significantly higher than those of Group C and Group DM+C(P=0.001, P<0.001).CONCLUSION: Adiponutrin and pannexin 1, which play an important role in the pathophysiology of diabetes and obesity, and have a regulatory role in hyperglycemia and insulin resistance.The measurement of adiponutrin and pannexin 1 levels may support clinicians in determining the risk of DR development.
基金This study was supported by the National Natural Science Foundation of China,Nos.31900718(to ZYW),31872773(to GC)the National Key Research and Development Program of China,No.2017YFA0104704(to GC)+2 种基金Basic Research Program of the Education Department of Jiangsu Province of China,Nos.19KJB180024(to ZYW),18KJB180020(to WXS)Postdoctoral Science Foundation of China,No.2019M651925(to ZYW),Jiangsu Students’Platform for Innovation and Entrepreneurship Training Program of China,No.201810304031Z(to YJD)Six Talent Peaks Project in Jiangsu Province of China,No.WSN-007(to WXS).
文摘Pannexin 1(Panx 1),as a large-pore membrane channel,is highly permeable to ATP and other signaling molecules.Previous studies have demonstrated the expression of Panx 1 in the nervous system,including astrocytes,microglia,and neurons.However,the distribution and function of Panx 1 in the peripheral nervous system are not clear.Blocking the function of Panx 1 pharmacologically(carbenoxolone and probenecid)or with small interfering RNA targeting pannexins can greatly reduce hypotonicity-induced ATP release.Treatment of Schwann cells with a Ras homolog family member(Rho)GTPase inhibitor and small interfering RNA targeting Rho or cytoskeleton disrupting agents,such as nocodazole or cytochalasin D,revealed that hypotonicity-induced ATP release depended on intracellular RhoA and the cytoskeleton.These findings suggest that Panx 1 participates in ATP release in Schwann cells by regulating RhoA and the cytoskeleton arrangement.This study was approved by the Animal Ethics Committee of Nantong University,China(No.S20180806-002)on August 5,2018.
基金Research in the Swayne lab was supported by operating grants to LAS from the Natural Sciences and Engineering Research Council of Canada(NSERC Discovery Grant)the Canadian Institutes of Health Research(CIHR Grant MOP142215)+5 种基金The Scottish Rite Charitable Foundation of Canada and the University of Victoria Division of Medical Sciencesby infrastructure grants from the Canadian Foundation for Innovation(CFI)the British Columbia Knowledge Development Fund(BCKDF)supported by a Michael Smith Foundation for Health Research and British Columbia Schizophrenia Society Foundation Scholar Awardsupported by a University of Victoria Fellowship Graduate Awardsupported by a Vanier Canada Graduate Scholarship(NSERC)
文摘We recently reported that targeted deletion of Pannexin 1 in neural precursor cells of the ventricular zone impairs the maintenance of these cells in healthy and stroke-injured brain. Here we frame this exciting new finding in the context of our previous studies on Pannexin 1 in neural precursors as well as the close rela- tionship between Pannexin 1 and purinergic receptors established by other groups. Moreover, we identify important gaps in our understanding of Pannexin 1 in neural precursor cell biology in terms of the under- lying molecular mechanisms and functional/behavioural outcomes.