20 April 2017 : Laboratory Research
Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined Signaling Route Would Induce Alternative Consideration to Previous ConceptionsGuojun Tong1ABCDEF, Yue Meng2ABCDEF, Song Hao1ABCD, Shaoyu Hu1ABCD, Youhua He1BCD, Wenjuan Yan3AEF, Dehong Yang1ACDEFG*
Med Sci Monit 2017; 23:1896-1906
BACKGROUND: Parathyroid hormone (PTH) is an effective anti-osteoporosis agent, after binding to its receptor PTHR1, several signaling pathways, including cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are initiated through G proteins; with the cAMP/PKA pathway as the major pathway. Earlier studies have reported that PTHR1 might also activate PKC via a PLC-independent mechanism, but this pathway remains unclear.
MATERIAL AND METHODS: In HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then assays for cell apoptosis, cell differentiation, alkaline phosphatase activity, and mineralization were performed.
RESULTS: The FRET analysis found that PTH(1–34), [G1,R19]PTH(1–34) (GR(1–34), and [G1,R19]PTH(1–28) (GR(1–28) were all activated by PKC. The PKC activation ability of GR(1–28) was blocked by cAMP inhibitor (Rp-cAMP) and rescued with the addition of active PKA-α and PKA-β. The PKC activation ability of GR(1–34) was partially inhibited by Rp-cAMP. In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was regulated by GR(1–28) were significantly changed by the pan-PKC inhibitor Go6983. After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG were differentially regulated by GR(1–28) or GR(1–34), and the difference was blunted by Go6983. PTH(1–34), GR(1–28), and GR(1–34) significantly decreased early apoptosis and augmented osteoblastic differentiation in accordance with the activities of PKA and PKC.
CONCLUSIONS: PLC-independent PKC activation induced by PTH could be divided into two potential mechanisms: one was PKA-dependent and associated with PTH(1–28); the other was PKA-independent and associated with PTH(29–34). We also found that PTH could activate PLC-independent PKC via PKA-dependent mechanisms.
Keywords: Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Parathyroid Hormone, Phosphoinositide Phospholipase C, Protein Kinase C
01 May 2022 : EditorialEditorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19
Med Sci Monit 2022; 28:e937048
04 May 2022 : Clinical ResearchEffects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936069
22 April 2022 : Clinical ResearchFactors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)
Med Sci Monit In Press; DOI: 10.12659/MSM.936547
17 May 2022 : Clinical ResearchClinical Application of C-TIRADS Category and Contrast-Enhanced Ultrasound in Differential Diagnosis of Sol...
Med Sci Monit In Press; DOI: 10.12659/MSM.936368
17 May 2022 : Laboratory ResearchArtificial Dermal Scaffold Loaded with Platelet-Rich Plasma Promotes Wound Healing in Pigs by Favoring Angi...
Med Sci Monit In Press; DOI: 10.12659/MSM.936186
16 May 2022 : Clinical ResearchEarly Enteral Nutrition Can Reduce Incidence of Postoperative Hydrocephalus in Patients with Severe Hyperte...
Med Sci Monit In Press; DOI: 10.12659/MSM.935850
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
01 Nov 2020 : Review articleLong-Term Respiratory and Neurological Sequelae of COVID-19
Med Sci Monit 2020; 26:e928996