CALBINDINS DECREASED AFTER SPACE-FLIGHT

Exposure of the body to microgravity during space flight causes a seri es of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to a nalyze the expression of calbindin-D-28k and calbindin-D-9k in kidneys , small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, mode led weightlessness animals (tail suspension), and their controls. Expo sure to microgravity resulted in a significant and sustained decrease in calbindin-D-28k content in the kidney and calbindin-D-9k in the sma ll intestine of flight animals, as measured by enzyme-linked immunosor bent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combina tion with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestin e, and the expression of insulin in pancreas. There was a large decrea se of immunoreactivity in renal distal tubular cell-associated calbind in-D-28k and in intestinal absorptive cell-associated calbindin-D-9k o f space flight and modeled weightlessness animals compared with matche d controls. No consistent difference in pancreatic insulin immunoreact ivity between space flight, modeled weightlessness, and controls was o bserved. Regression analysis of results obtained by quantitative ICC a nd ELISA for space flight, modeled weightlessness animals, and their c ontrols demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins may contribute to the disor ders of Ca2+ metabolism induced by space flight.