title: Nesfatin-1 inhibits proliferation and enhances apoptosis of human adrenocortical H295R cells.
abstract: NUCB2/nesfatin and its proteolytically cleaved product nesfatin-1 are recently discovered anorexigenic hypothalamic neuroproteins involved in energy homeostasis. It is expressed both centrally and in peripheral tissues, and appears to have potent metabolic actions. NUCB2/nesfatin neurons are activated in response to stress. Central nesfatin-1 administration elevates circulating ACTH and corticosterone levels. Bilateral adrenalectomy increased NUCB2/nesfatin mRNA levels in rat paraventricular nuclei. To date, studies have not assessed the effects of nesfatin-1 stimulation on human adrenocortical cells. Therefore, we investigated the expression and effects of nesfatin-1 in a human adrenocortical cell model (H295R). Our findings demonstrate that NUCB2 and nesfatin-1 are expressed in human adrenal gland and human adrenocortical cells (H295R). Stimulation with nesfatin-1 inhibits the growth of H295R cells and promotes apoptosis, potentially via the involvement of Bax, BCL-XL and BCL-2 genes as well as ERK1/2, p38 and JNK1/2 signalling cascades. This has implications for understanding the role of NUCB2/nesfatin in adrenal zonal development. NUCB2/nesfatin may also be a therapeutic target for adrenal cancer. However, further studies using in vivo models are needed to clarify these concepts.
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Manjunath
authors: M
authors: Ramanjaneya
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Bee K
authors: BK
authors: Tan
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Marcin
authors: M
authors: Rucinski
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Mohamed
authors: M
authors: Kawan
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Jiamiao
authors: J
authors: Hu
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Jaspreet
authors: J
authors: Kaur
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Vanlata H
authors: VH
authors: Patel
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Ludwik K
authors: LK
authors: Malendowicz
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Hanna
authors: H
authors: Komarowska
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Hendrik
authors: H
authors: Lehnert
authors: Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal Medicine, University of Medical Sciences, 16 Karol Marcinkowski, Poznan, Poland1st Medical DepartmentUniversity of Lübeck Medical School, Lübeck, GermanyDepartment of DiabetesEndocrinology and Metabolism, University Hospital, Coventry CV2 2DX, UKAston Medical Research InstituteSchool of Life and Health Sciences, Aston University, Birmingham, UK Warwick Medical SchoolUniversity of Warwick, Coventry CV4 7AL, UKInterim Translational Research InstituteAcademic Health System, Hamad Medical Corporation, Doha, QatarDepartment of Obstetrics and GynaecologyBirmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UKDepartment of Histology and EmbryologyPoznan University of Medical Sciences, Poznan, PolandDepartment of EndocrinologyMetabolism and Internal 
authors: Harpal S
authors: HS
authors: Randeva
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D019254:Genes, bcl-2; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D000080866:Nucleobindins; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000235:genetics; D051020:bcl-X Protein / Q000235:genetics; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D010750:Phosphoproteins; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000098682:Steroidogenic Acute Regulatory Protein; D000450:Aldosterone; D006854:Hydrocortisone
keywords: NUCB2; adrenal cortex; apoptosis; nesfatin-1