The effect of 3-hydroxybutyrate and its derivatives on the growth of glial cells.
Sodium salts of D-3-hydroxybutyrate (D-3-HB), DL-3-hydroxybutyrate (DL-3-HB) and methyl (D)-3-hydroxybutyrate (M-3-HB), are derivatives of 3-hydroxybutyric acid (3-HB), a ketone body that is produced in vivo in animals including human. D-3-HB is the most common degradation product of microbial polyhydroxyalkanoates (PHA) that have been investigated for tissue engineering application. This study evaluated the in vitro effect of PHA degradation product 3-HB and its derivatives (collectively called 3-HB derivatives) on cell apoptosis and cytosolic Ca(2+) concentration of mouse glial cells. Results showed that the percentage of cells undergoing apoptosis decreased significantly in the presence of 3-HB and its derivatives as evidenced by flow cytometry. The in vitro study on cytosolic Ca(2+) concentration demonstrated that 3-HB derivatives dramatically elevated the cytosolic Ca(2+) concentration. Both the extracellular and intracellular Ca(2+) contributed as the sources of such Ca(2+) concentration elevation. The effect of 3-HB derivatives on cytosolic Ca(2+) concentration could be reduced by nitredipine, an L-type voltage-dependent calcium channel antagonist. In comparison, M-3-HB worked more efficiently than D-3-HB and DL-3-HB did as M-3-HB is more efficient in permeation into the cells. All results indicated that 3-HB derivatives had an inhibitory effect on cell apoptosis which is mediated by signaling pathways related to the elevation of cytosolic Ca(2+) concentration. This positive effect helps explain the biocompatibility observed for PHA, it also points to the possibility of 3-HB derivatives regardless of chirality to become an effective neural protective agent.
Xiao
Xiao-Qiang
XQ
Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China.
Zhao
Yan
Y
Chen
Guo-Qiang
GQ
D020155:3-Hydroxybutyric Acid / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology
D018696:Neuroprotective Agents; D002118:Calcium; D020155:3-Hydroxybutyric Acid